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Papers by Gary Lu

Blood

4059 Background: Approximately 5% of cancer patients treated with cytotoxic agents develop cytoge... more 4059 Background: Approximately 5% of cancer patients treated with cytotoxic agents develop cytogenetic abnormalities which can progress to therapy-related myeloid malignancies over time. Acquired cytogenetic clones (ACC) have been incidentally observed in patients treated for multiple myeloma, yet their long-term clinical significance is not well defined. Patients and Methods: We performed a retrospective review of patients treated for multiple myeloma at the University of Texas MD Anderson Cancer Center over an 11-year period from 6/2001 to 6/2012. Patients with acquired cytogenetic abnormalities were identified and corresponding bone marrow biopsies at the time of detection were evaluated for the presence of therapy-related myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML). Among these cases, patients with abnormal cytogenetic clones confirmed by karyotyping and/or FISH but without morphologic or clinical evidence of t-MDS/AML were classified as having silent ACC ...

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Dec 13, 2016

The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outc... more The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outcome in patients with multiple myeloma (MM). However, there are limited data on the outcome of patients with CKS1B amplification after a single high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively evaluated the outcome of patients with CKS1B amplification who received an auto-HCT between June 2012 and July 2014 at our institution. We identified 58 patients with MM and CKS1B gene amplification detected by fluorescent in situ hybridization (FISH). We compared their outcomes with a propensity score matched control group of 58 patients without CKS1B amplification that were treated at approximately the same time. The primary objective was to compare the progression-free (PFS) and overall survival (OS) between the CKS1B and the control group. Stratified log-rank test with the matched pairs as strata and double robust estimation under the C...

Journal of Obstetrics and Gynaecology Research, 2016

The two cases in this report had intermittent massive vaginal bleeding with a distant history of ... more The two cases in this report had intermittent massive vaginal bleeding with a distant history of cesarean delivery. Such severe bleeding was life-threating but was eventually cured by surgical management. To the best of our knowledge, this is the second report of cases of tardive vaginal bleeding caused by abnormal blood vessels embedded within cesarean scars. The two new cases in this report suggest a novel cause of tardive vaginal bleeding, which should bring our special attention to post-cesarean clinical practice.

Beijing Da Xue Xue Bao Yi Xue Ban Journal of Peking University Health Sciences, Mar 1, 2006

To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LP... more To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LPDs). Cases were collected from the clinical laboratory diagnosis database at USLabs/LabCorp over the past two years (2002 to 2004). Cases that showed deletions in the long arm of chromosome 7 were then reviewed. Interstitial deletions in the long arm of chromosome 7 were further investigated according to the indications for clinical laboratory studies and flow cytometry findings. The final clinical diagnosis for each case was obtained from the referring physician. A total of 19,483 cases were included in this series. Eighty-five cases were observed to have either terminal or interstitial deletion in the long arm of chromosome 7. Of the 85 cases, 46 had interstitial deletions accounting for 54.1% of the 7q deletions combined. B-LPDs were found in 10 of the 46 cases, accounting for 21.7%. The B-LPDs associated with 7q interstitial deletions were diverse, including B-cell chronic lymphocytic leukemia (B-CLL) in five cases. The deleted region in the long arm of chromosome 7 in the 10 cases associated with B-LPDs was solely confined to the 7q22-q32 region. (1) The frequency of 7q interstitial deletions associated with B-LPDs is substantially high; (2) 7q interstitial deletions are not uncommon in B-CLL.

American Journal of Hematology, 2016

TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outco... more TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n=111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P=0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P=0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P=0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P<0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P<0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P<0.001) and relapsed disease at auto-HCT (hazard ratio 2.0, 95% confidence interval 1.2-3.4, P=0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto-HCT, TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. This article is protected by copyright. All rights reserved.

Journal of hematology & oncology, Jan 29, 2015

Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoid malignancy worldwide. A... more Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoid malignancy worldwide. Approximately 5 % of cases of DLBCL are so-called double-hit lymphomas (DHL), defined by a chromosomal translocation or rearrangement involving MYC/8q24.2 in combination with another recurrent breakpoint, usually BCL2/18q21.3. Patients with MYC/BCL2 DHL are resistant to standard front-line therapy, and currently, there is no consensus for a therapeutic strategy to treat these patients. Lack of clinically relevant or validated human experimental DHL models of any type that would improve our understanding of the biologic basis of MYC/BCL2 DHL pathophysiology continues to hamper identification of valid therapeutic targets. We describe a unique MYC/BCL2 DHL cell line with morphologic features of DLBCL that we have established, designated as RC. We used tissue culture techniques to establish the RC cell line from primary DLBCL cells. We also utilized molecular and cellular biological technique...

American Chinese Journal of Medicine and Science, 2012

Acute myeloid leukemia (AML) is a heterogeneous group of diseases with a multitude of molecular g... more Acute myeloid leukemia (AML) is a heterogeneous group of diseases with a multitude of molecular genetic aberrations and variable clinical outcome. Clonal chromosomal abnormalities have been identified in over 50% of AML cases, and have been regarded as one of the most important prognostic markers. We present a case of a 56-year-old Hispanic man with AML with minimal differentiation. Morphologically, the bone marrow was hypercellular with trilineage hypoplasia and 80% blasts. Flow cytometry analysis showed that the blasts were of myeloid immunophenotype. Conventional cytogenetic analysis showed t(1;3)(p36;p21) as the sole cytogenetic abnormality in 5 of 20 metaphases analyzed. The patient received daunorubicin and cytarabine, and achieved first remission. He relapsed 4 months later, and was treated with fludarabine, cytarabine, idarubicin, and G-CSF, and consolidated with high-dose cytarabine. He then received matched related stem cell transplantation. However, the disease relapsed again, and the patient died 11 months after initial diagnosis. To our best knowledge, this is the first report of t(1;3)(p36;p21) as the sole cytogenetic abnormality.

International journal of clinical and experimental pathology

Trisomy 11 (+11) as an isolated abnormality is a rare event in patients with acute myeloid leukem... more Trisomy 11 (+11) as an isolated abnormality is a rare event in patients with acute myeloid leukemia (AML) and is associated with poor prognosis. We describe the clinicopathologic features of 18 AML patients with isolated +11 and their mutation status of NPM1, FLT3, NRAS ,KRAS, and KIT. Fourteen patients had de novo AML and 4 patients had a history of myelodysplastic syndrome (MDS). Fifteen patients had a progressive clinical course with refractory or relapsed disease. The median overall survival was 5 months (range, 2 to 48 months). Only 1 patient achieved complete remission after undergoing stem cell transplantation. The bone marrow median blast count was 65% (range, 22 to 86) and 14 patients had blasts >50%. The most common type of AML was AML without maturation (7 patients) classified by the World Health Organization classification system, or M1 (10 patients) by the French-American-British (FAB) system. FLT3 mutations were detected in 3 of 15 (20%) cases tested. RAS mutation was present in 1 of 16 (6%) cases and there was no evidence of NPM1 of KIT mutations (each tested in 12 cases). Our findings confirm previous reports that isolated +11 is associated with a poor prognosis in patients with AML and tends to be associated with FAB-M1 morphologic features. No evidence of NPM1 or KIT mutations were identified.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, Jan 8, 2015

Deletion 20q (Del(20q)), a common cytogenetic abnormality in myeloid neoplasms, is rare in chroni... more Deletion 20q (Del(20q)), a common cytogenetic abnormality in myeloid neoplasms, is rare in chronic lymphocytic leukemia. We report 64 patients with chronic lymphocytic leukemia and del(20q), as the sole abnormality in 40, a stemline abnormality in 21, and a secondary abnormality in 3 cases. Fluorescence in situ hybridization (FISH) analysis revealed an additional high-risk abnormality, del(11q) or del(17p), in 25/64 (39%) cases. In most cases, the leukemic cells showed atypical cytologic features, unmutated IGHV (immunoglobulin heavy-chain variable region) genes, and ZAP70 positivity. The del(20q) was detected only after chemotherapy in all 27 cases with initial karyotypes available. With a median follow-up of 90 months, 30 patients (47%) died, most as a direct consequence of chronic lymphocytic leukemia. Eight patients developed a therapy-related myeloid neoplasm, seven with a complex karyotype. Combined morphologic and FISH analysis for del(20q) performed in 12 cases without morph...

Clinical Lymphoma Myeloma and Leukemia, 2015

Primary myelofibrosis (PMF) is a rare myeloproliferative stem cell disorder. The genomic features... more Primary myelofibrosis (PMF) is a rare myeloproliferative stem cell disorder. The genomic features in PMF are poorly understood. Characterization of genomic alternations in PMF helps to determine their association with clinicopathologic features for further therapeutic implications. In this retrospective study, we investigated genomic changes using array-based comparative genomic hybridization (aCGH) in 17 PMF patients with isolated del(13q) and confirmed our aCGH findings with quantitative polymerase chain reaction (PCR) assay. We also compared the clinicopathologic features of patients with del(13q) (n = 17) with those of patients with a normal karyotype (NK) (n = 26). Clinicopathologically, del(13q) PMF patients had significantly higher blast counts (P = .03) than did NK patients, who had significantly higher marrow cellularity (P = .02). The degree of bone marrow fibrosis of PMF-3 was higher in the del(13q) group than in the NK group. Splenomegaly was present significantly more often in the del(13q) PMF group than in the NK group (P = .03). Genomically, the Janus Kinase 2 V617F mutation was observed less often in del(13q) PMF patients (P = .07). The common deleted region in del(13q) was confined to 13q13-13q14.3 according to G-band karyotyping, demonstrating a minimal deleted region (MDR) of 15.323 Mb, identified using aCGH. The tumor suppressor genes, Retinoblastoma, Forkhead box protein O1, and Succinyl -CoA ligase [ADP-forming] subunit beta in the MDR were deleted, confirmed using real-time PCR to confirm our aCGH findings. Accurate molecular characterization of del(13q) in PMF using aCGH and quantitative PCR provided further insight to define the MDR and analyze the genomic changes in del(13q) PMF patients.

Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences, Jan 18, 2009

Rearrangements involving chromosome region at 12p13 are common abnormalities in hematological mal... more Rearrangements involving chromosome region at 12p13 are common abnormalities in hematological malignancies, including myeloid and lymphoid types. ETV6 gene is usually involved in the 12p13 region. ETV6 rearrangements are more often observed in acute lymphoblastic leukemia than in acute myeloid leukemia (AML), where ETV6 gene deletions are more common than rearrangements. Here, we report an AML case with the recurrent t(10; 12) (q24; p13) as the sole abnormality. Fluorescence in situ hybridization with mapping back to metaphases confirmed that the ETV6 gene splits, and rearranges with a locus at 10q24. In review of the literature, this is the first report of AML case with the novel abnormality as the sole change. Complete laboratory findings from bone marrow examination, flow cytometry analysis, cytogenetic studies, molecular analysis, and clinical features are also described in the report.

Biology of Blood and Marrow Transplantation, 2015

Clinical lymphoma, myeloma & leukemia, 2014

Donor cell leukemia (DCL) is a rare condition defined as leukemia or myelodysplasia that develops... more Donor cell leukemia (DCL) is a rare condition defined as leukemia or myelodysplasia that develops in grafted donor cells. To the authors’ knowledge, this report presents the first cases of DCL with r(7) abnormality (ring chromosome 7). Although abnormalities of chromosome 7 are common in acute myeloid leukemia and myelodysplastic syndrome, detection of r(7) and recognition of its origin can be challenging. This is also the first report of del(12p) (deletion of 12p) resulting in ETV6 (ets translocation variant gene 6) deletion in DCL. Progression of disease in the patient with del(12p)/ ETV6, from myelodysplastic syndrome to acute myeloid leukemia, suggests that del(12p)/ETV6 may play an important role in leukemia transformation in DCL.

Leukemia & lymphoma, Jan 18, 2014

The proto-oncogene c-MYC is rearranged in about 15% of patients with multiple myeloma (MM). We id... more The proto-oncogene c-MYC is rearranged in about 15% of patients with multiple myeloma (MM). We identified 23 patients with MM and c-MYC. Primary objectives were to describe the clinical characteristics, response to therapy, progression-free survival and overall survival (OS). Twelve out of twenty-three patients presented with or progressed to either plasma cell leukemia (PCL) and/or extramedullary disease (EMD). Induction therapy consisted of an immunomodulatory, proteasome inhibitor-based or conventional chemotherapy regimen. Fifteen patients achieved a partial response and three achieved a very good partial response. Sixteen patients received an autologous and one patient an allogeneic hematopoietic stem cell transplant. Median OS from diagnosis was 20.2 months. Patients with PCL or EMD had significantly shorter OS (15.5 vs. 40.4 months, p = 0.0005). This is the first report describing the clinical characteristics of patients with MM and c-MYC. These abnormalities are associated w...

Clinical lymphoma, myeloma & leukemia, Jan 12, 2014

Follicular lymphoma (FL) is the second most common B-cell non-Hodgkin lymphoma worldwide. In most... more Follicular lymphoma (FL) is the second most common B-cell non-Hodgkin lymphoma worldwide. In most patients, the disease is diagnosed at advanced stages and cannot be cured using conventional therapeutic approaches. To assess the role of cytogenetic abnormalities in therapy-related myeloid neoplasms (tMNs), we studied the clinicopathologic and cytogenetic features of treated FL patients who subsequently developed a new acquired cytogenetic clone (ACC). Twenty-five treated FL patients developed new cytogenetic abnormalities from 2009 to 2012. Patients were divided into 3 groups based on the presence and absence of tMNs: group 1, ACC without tMNs after a median follow-up of 15 months; group 2, ACC with possible tMN after silent ACC detection; group 3, tMNs present at the first ACC detection. The most frequent cytogenetic aberrations involved chromosome 7. Compared with group 1, group 3 had significantly greater size of ACC, higher frequency of chromosome 7 aberrations, more likely show...

International journal of clinical and experimental pathology, 2014

Rearrangements of the MLL gene located at chromosome 11q23 are common chromosomal abnormalities a... more Rearrangements of the MLL gene located at chromosome 11q23 are common chromosomal abnormalities associated with acute leukemias. In vast majority of cases with MLL gene rearrangements, only one chromosome 11 or a single MLL allele got involved. We report two very unusual cases of myeloid neoplasms with homozygous inv(11)(q21q23) and biallelic MLL rearrangement. Both patients, a 12-year old boy and a 29-year old woman, presented initially with T lymphoblastic leukemia/lymphoma (T-ALL), achieved complete remission with intensive chemotherapy, then recurred as acute myeloid leukemia in one patient and therapy-related myelodysplastic syndromes in the other patient, 24 and 15 months after initial T-ALL diagnosis, respectively. In both cases, biallelic MLL gene rearrangements were confirmed by fluorescence in situ hybridization. Mastermind like 2 gene was identified as MLL partner gene in one case. To our knowledge, homozygous inv(11)(q21q23) with two MLL genes rearrangement are extremely...

Biology of Blood and Marrow Transplantation, 2015

Clinical Lymphoma Myeloma and Leukemia, 2013

Blood

4059 Background: Approximately 5% of cancer patients treated with cytotoxic agents develop cytoge... more 4059 Background: Approximately 5% of cancer patients treated with cytotoxic agents develop cytogenetic abnormalities which can progress to therapy-related myeloid malignancies over time. Acquired cytogenetic clones (ACC) have been incidentally observed in patients treated for multiple myeloma, yet their long-term clinical significance is not well defined. Patients and Methods: We performed a retrospective review of patients treated for multiple myeloma at the University of Texas MD Anderson Cancer Center over an 11-year period from 6/2001 to 6/2012. Patients with acquired cytogenetic abnormalities were identified and corresponding bone marrow biopsies at the time of detection were evaluated for the presence of therapy-related myelodysplastic syndrome (t-MDS) or acute myeloid leukemia (t-AML). Among these cases, patients with abnormal cytogenetic clones confirmed by karyotyping and/or FISH but without morphologic or clinical evidence of t-MDS/AML were classified as having silent ACC ...

Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, Dec 13, 2016

The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outc... more The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outcome in patients with multiple myeloma (MM). However, there are limited data on the outcome of patients with CKS1B amplification after a single high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively evaluated the outcome of patients with CKS1B amplification who received an auto-HCT between June 2012 and July 2014 at our institution. We identified 58 patients with MM and CKS1B gene amplification detected by fluorescent in situ hybridization (FISH). We compared their outcomes with a propensity score matched control group of 58 patients without CKS1B amplification that were treated at approximately the same time. The primary objective was to compare the progression-free (PFS) and overall survival (OS) between the CKS1B and the control group. Stratified log-rank test with the matched pairs as strata and double robust estimation under the C...

Journal of Obstetrics and Gynaecology Research, 2016

The two cases in this report had intermittent massive vaginal bleeding with a distant history of ... more The two cases in this report had intermittent massive vaginal bleeding with a distant history of cesarean delivery. Such severe bleeding was life-threating but was eventually cured by surgical management. To the best of our knowledge, this is the second report of cases of tardive vaginal bleeding caused by abnormal blood vessels embedded within cesarean scars. The two new cases in this report suggest a novel cause of tardive vaginal bleeding, which should bring our special attention to post-cesarean clinical practice.

Beijing Da Xue Xue Bao Yi Xue Ban Journal of Peking University Health Sciences, Mar 1, 2006

To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LP... more To study the frequency of interstitial 7q deletions in B-cell lymphoproliferative disorders (B-LPDs). Cases were collected from the clinical laboratory diagnosis database at USLabs/LabCorp over the past two years (2002 to 2004). Cases that showed deletions in the long arm of chromosome 7 were then reviewed. Interstitial deletions in the long arm of chromosome 7 were further investigated according to the indications for clinical laboratory studies and flow cytometry findings. The final clinical diagnosis for each case was obtained from the referring physician. A total of 19,483 cases were included in this series. Eighty-five cases were observed to have either terminal or interstitial deletion in the long arm of chromosome 7. Of the 85 cases, 46 had interstitial deletions accounting for 54.1% of the 7q deletions combined. B-LPDs were found in 10 of the 46 cases, accounting for 21.7%. The B-LPDs associated with 7q interstitial deletions were diverse, including B-cell chronic lymphocytic leukemia (B-CLL) in five cases. The deleted region in the long arm of chromosome 7 in the 10 cases associated with B-LPDs was solely confined to the 7q22-q32 region. (1) The frequency of 7q interstitial deletions associated with B-LPDs is substantially high; (2) 7q interstitial deletions are not uncommon in B-CLL.

American Journal of Hematology, 2016

TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outco... more TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n=111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P=0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P=0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P=0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P<0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P<0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P<0.001) and relapsed disease at auto-HCT (hazard ratio 2.0, 95% confidence interval 1.2-3.4, P=0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto-HCT, TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. This article is protected by copyright. All rights reserved.

Journal of hematology & oncology, Jan 29, 2015

Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoid malignancy worldwide. A... more Diffuse large B cell lymphoma (DLBCL) is the most common type of lymphoid malignancy worldwide. Approximately 5 % of cases of DLBCL are so-called double-hit lymphomas (DHL), defined by a chromosomal translocation or rearrangement involving MYC/8q24.2 in combination with another recurrent breakpoint, usually BCL2/18q21.3. Patients with MYC/BCL2 DHL are resistant to standard front-line therapy, and currently, there is no consensus for a therapeutic strategy to treat these patients. Lack of clinically relevant or validated human experimental DHL models of any type that would improve our understanding of the biologic basis of MYC/BCL2 DHL pathophysiology continues to hamper identification of valid therapeutic targets. We describe a unique MYC/BCL2 DHL cell line with morphologic features of DLBCL that we have established, designated as RC. We used tissue culture techniques to establish the RC cell line from primary DLBCL cells. We also utilized molecular and cellular biological technique...

American Chinese Journal of Medicine and Science, 2012

Acute myeloid leukemia (AML) is a heterogeneous group of diseases with a multitude of molecular g... more Acute myeloid leukemia (AML) is a heterogeneous group of diseases with a multitude of molecular genetic aberrations and variable clinical outcome. Clonal chromosomal abnormalities have been identified in over 50% of AML cases, and have been regarded as one of the most important prognostic markers. We present a case of a 56-year-old Hispanic man with AML with minimal differentiation. Morphologically, the bone marrow was hypercellular with trilineage hypoplasia and 80% blasts. Flow cytometry analysis showed that the blasts were of myeloid immunophenotype. Conventional cytogenetic analysis showed t(1;3)(p36;p21) as the sole cytogenetic abnormality in 5 of 20 metaphases analyzed. The patient received daunorubicin and cytarabine, and achieved first remission. He relapsed 4 months later, and was treated with fludarabine, cytarabine, idarubicin, and G-CSF, and consolidated with high-dose cytarabine. He then received matched related stem cell transplantation. However, the disease relapsed again, and the patient died 11 months after initial diagnosis. To our best knowledge, this is the first report of t(1;3)(p36;p21) as the sole cytogenetic abnormality.

International journal of clinical and experimental pathology

Trisomy 11 (+11) as an isolated abnormality is a rare event in patients with acute myeloid leukem... more Trisomy 11 (+11) as an isolated abnormality is a rare event in patients with acute myeloid leukemia (AML) and is associated with poor prognosis. We describe the clinicopathologic features of 18 AML patients with isolated +11 and their mutation status of NPM1, FLT3, NRAS ,KRAS, and KIT. Fourteen patients had de novo AML and 4 patients had a history of myelodysplastic syndrome (MDS). Fifteen patients had a progressive clinical course with refractory or relapsed disease. The median overall survival was 5 months (range, 2 to 48 months). Only 1 patient achieved complete remission after undergoing stem cell transplantation. The bone marrow median blast count was 65% (range, 22 to 86) and 14 patients had blasts >50%. The most common type of AML was AML without maturation (7 patients) classified by the World Health Organization classification system, or M1 (10 patients) by the French-American-British (FAB) system. FLT3 mutations were detected in 3 of 15 (20%) cases tested. RAS mutation was present in 1 of 16 (6%) cases and there was no evidence of NPM1 of KIT mutations (each tested in 12 cases). Our findings confirm previous reports that isolated +11 is associated with a poor prognosis in patients with AML and tends to be associated with FAB-M1 morphologic features. No evidence of NPM1 or KIT mutations were identified.

Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, Jan 8, 2015

Deletion 20q (Del(20q)), a common cytogenetic abnormality in myeloid neoplasms, is rare in chroni... more Deletion 20q (Del(20q)), a common cytogenetic abnormality in myeloid neoplasms, is rare in chronic lymphocytic leukemia. We report 64 patients with chronic lymphocytic leukemia and del(20q), as the sole abnormality in 40, a stemline abnormality in 21, and a secondary abnormality in 3 cases. Fluorescence in situ hybridization (FISH) analysis revealed an additional high-risk abnormality, del(11q) or del(17p), in 25/64 (39%) cases. In most cases, the leukemic cells showed atypical cytologic features, unmutated IGHV (immunoglobulin heavy-chain variable region) genes, and ZAP70 positivity. The del(20q) was detected only after chemotherapy in all 27 cases with initial karyotypes available. With a median follow-up of 90 months, 30 patients (47%) died, most as a direct consequence of chronic lymphocytic leukemia. Eight patients developed a therapy-related myeloid neoplasm, seven with a complex karyotype. Combined morphologic and FISH analysis for del(20q) performed in 12 cases without morph...

Clinical Lymphoma Myeloma and Leukemia, 2015

Primary myelofibrosis (PMF) is a rare myeloproliferative stem cell disorder. The genomic features... more Primary myelofibrosis (PMF) is a rare myeloproliferative stem cell disorder. The genomic features in PMF are poorly understood. Characterization of genomic alternations in PMF helps to determine their association with clinicopathologic features for further therapeutic implications. In this retrospective study, we investigated genomic changes using array-based comparative genomic hybridization (aCGH) in 17 PMF patients with isolated del(13q) and confirmed our aCGH findings with quantitative polymerase chain reaction (PCR) assay. We also compared the clinicopathologic features of patients with del(13q) (n = 17) with those of patients with a normal karyotype (NK) (n = 26). Clinicopathologically, del(13q) PMF patients had significantly higher blast counts (P = .03) than did NK patients, who had significantly higher marrow cellularity (P = .02). The degree of bone marrow fibrosis of PMF-3 was higher in the del(13q) group than in the NK group. Splenomegaly was present significantly more often in the del(13q) PMF group than in the NK group (P = .03). Genomically, the Janus Kinase 2 V617F mutation was observed less often in del(13q) PMF patients (P = .07). The common deleted region in del(13q) was confined to 13q13-13q14.3 according to G-band karyotyping, demonstrating a minimal deleted region (MDR) of 15.323 Mb, identified using aCGH. The tumor suppressor genes, Retinoblastoma, Forkhead box protein O1, and Succinyl -CoA ligase [ADP-forming] subunit beta in the MDR were deleted, confirmed using real-time PCR to confirm our aCGH findings. Accurate molecular characterization of del(13q) in PMF using aCGH and quantitative PCR provided further insight to define the MDR and analyze the genomic changes in del(13q) PMF patients.

Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences, Jan 18, 2009

Rearrangements involving chromosome region at 12p13 are common abnormalities in hematological mal... more Rearrangements involving chromosome region at 12p13 are common abnormalities in hematological malignancies, including myeloid and lymphoid types. ETV6 gene is usually involved in the 12p13 region. ETV6 rearrangements are more often observed in acute lymphoblastic leukemia than in acute myeloid leukemia (AML), where ETV6 gene deletions are more common than rearrangements. Here, we report an AML case with the recurrent t(10; 12) (q24; p13) as the sole abnormality. Fluorescence in situ hybridization with mapping back to metaphases confirmed that the ETV6 gene splits, and rearranges with a locus at 10q24. In review of the literature, this is the first report of AML case with the novel abnormality as the sole change. Complete laboratory findings from bone marrow examination, flow cytometry analysis, cytogenetic studies, molecular analysis, and clinical features are also described in the report.

Biology of Blood and Marrow Transplantation, 2015

Clinical lymphoma, myeloma & leukemia, 2014

Donor cell leukemia (DCL) is a rare condition defined as leukemia or myelodysplasia that develops... more Donor cell leukemia (DCL) is a rare condition defined as leukemia or myelodysplasia that develops in grafted donor cells. To the authors’ knowledge, this report presents the first cases of DCL with r(7) abnormality (ring chromosome 7). Although abnormalities of chromosome 7 are common in acute myeloid leukemia and myelodysplastic syndrome, detection of r(7) and recognition of its origin can be challenging. This is also the first report of del(12p) (deletion of 12p) resulting in ETV6 (ets translocation variant gene 6) deletion in DCL. Progression of disease in the patient with del(12p)/ ETV6, from myelodysplastic syndrome to acute myeloid leukemia, suggests that del(12p)/ETV6 may play an important role in leukemia transformation in DCL.

Leukemia & lymphoma, Jan 18, 2014

The proto-oncogene c-MYC is rearranged in about 15% of patients with multiple myeloma (MM). We id... more The proto-oncogene c-MYC is rearranged in about 15% of patients with multiple myeloma (MM). We identified 23 patients with MM and c-MYC. Primary objectives were to describe the clinical characteristics, response to therapy, progression-free survival and overall survival (OS). Twelve out of twenty-three patients presented with or progressed to either plasma cell leukemia (PCL) and/or extramedullary disease (EMD). Induction therapy consisted of an immunomodulatory, proteasome inhibitor-based or conventional chemotherapy regimen. Fifteen patients achieved a partial response and three achieved a very good partial response. Sixteen patients received an autologous and one patient an allogeneic hematopoietic stem cell transplant. Median OS from diagnosis was 20.2 months. Patients with PCL or EMD had significantly shorter OS (15.5 vs. 40.4 months, p = 0.0005). This is the first report describing the clinical characteristics of patients with MM and c-MYC. These abnormalities are associated w...

Clinical lymphoma, myeloma & leukemia, Jan 12, 2014

Follicular lymphoma (FL) is the second most common B-cell non-Hodgkin lymphoma worldwide. In most... more Follicular lymphoma (FL) is the second most common B-cell non-Hodgkin lymphoma worldwide. In most patients, the disease is diagnosed at advanced stages and cannot be cured using conventional therapeutic approaches. To assess the role of cytogenetic abnormalities in therapy-related myeloid neoplasms (tMNs), we studied the clinicopathologic and cytogenetic features of treated FL patients who subsequently developed a new acquired cytogenetic clone (ACC). Twenty-five treated FL patients developed new cytogenetic abnormalities from 2009 to 2012. Patients were divided into 3 groups based on the presence and absence of tMNs: group 1, ACC without tMNs after a median follow-up of 15 months; group 2, ACC with possible tMN after silent ACC detection; group 3, tMNs present at the first ACC detection. The most frequent cytogenetic aberrations involved chromosome 7. Compared with group 1, group 3 had significantly greater size of ACC, higher frequency of chromosome 7 aberrations, more likely show...

International journal of clinical and experimental pathology, 2014

Rearrangements of the MLL gene located at chromosome 11q23 are common chromosomal abnormalities a... more Rearrangements of the MLL gene located at chromosome 11q23 are common chromosomal abnormalities associated with acute leukemias. In vast majority of cases with MLL gene rearrangements, only one chromosome 11 or a single MLL allele got involved. We report two very unusual cases of myeloid neoplasms with homozygous inv(11)(q21q23) and biallelic MLL rearrangement. Both patients, a 12-year old boy and a 29-year old woman, presented initially with T lymphoblastic leukemia/lymphoma (T-ALL), achieved complete remission with intensive chemotherapy, then recurred as acute myeloid leukemia in one patient and therapy-related myelodysplastic syndromes in the other patient, 24 and 15 months after initial T-ALL diagnosis, respectively. In both cases, biallelic MLL gene rearrangements were confirmed by fluorescence in situ hybridization. Mastermind like 2 gene was identified as MLL partner gene in one case. To our knowledge, homozygous inv(11)(q21q23) with two MLL genes rearrangement are extremely...

Biology of Blood and Marrow Transplantation, 2015

Clinical Lymphoma Myeloma and Leukemia, 2013