Frédéric Lambert - Academia.edu (original) (raw)
Papers by Frédéric Lambert
The American Journal of Surgical Pathology, Jan 11, 2021
Cells
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Gemcitabine is th... more Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Gemcitabine is the first-line therapy for PDAC, but gemcitabine resistance is a major impediment to achieving satisfactory clinical outcomes. This study investigated whether methylglyoxal (MG), an oncometabolite spontaneously formed as a by-product of glycolysis, notably favors PDAC resistance to gemcitabine. We observed that human PDAC tumors expressing elevated levels of glycolytic enzymes together with high levels of glyoxalase 1 (GLO1), the major MG-detoxifying enzyme, present with a poor prognosis. Next, we showed that glycolysis and subsequent MG stress are triggered in PDAC cells rendered resistant to gemcitabine when compared with parental cells. In fact, acquired resistance, following short and long-term gemcitabine challenges, correlated with the upregulation of GLUT1, LDHA, GLO1, and the accumulation of MG protein adducts. We showed that MG-mediated activation of heat shock response is, at lea...
European Journal of Haematology, 2013
To the Editor: Refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T) is a rare en... more To the Editor: Refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T) is a rare entity and is defined as an overlap syndrome with clinical and morphologic features of both myelodysplastic syndrome (MDS) and BCR-ABL-negative myeloproliferative neoplasm, including marked thrombocytosis associated with abnormal megakaryocytes (1). Mutations in the Janus Kinase 2 gene (JAK2) and/or Splicing Factor 3B subunit 1 (SF3B1) gene have been detected in 50-70% of patients with RARS-T (2-4). The presence of such a mutation in either JAK2 or SF3B1 was associated with a better overall survival in a recent European study (5). Because of its activity in lower-risk MDS with or without the 5q-cytogenetic abnormality (6) and in myelofibrosis (7), lenalidomide treatment has been given with success in two patients with RARS-T. In this letter, we would like to report a case of RARS-T that was successfully treated by lenalidomide. An 84-years-old woman was referred for unexplained normocytic anaemia (Hb 7.7 g/dL) with marked thrombocytosis
American Journal of Surgical Pathology, 2021
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an indolent small B-cell neo... more Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an indolent small B-cell neoplasm that may transform into a clinically aggressive disease, namely Richter syndrome, usually as diffuse large B-cell lymphoma. Besides, CLL/SLL encompasses an increased risk of developing other secondary cancers, including a variety of T-cell lymphomas, often of the anaplastic large-cell type or with a cytotoxic phenotype. Here, we report a small series of patients with composite lymphomas consisting of CLL/SLL and angioimmunoblastic T-cell lymphoma (AITL), a hitherto unrecognized association. The 3 patients (1 male/2 females, 68 to 83 y) presented with high-grade-type symptoms. One patient was clinically suspicious for Richter syndrome, in the others CLL/SLL and AITL were concomitant de novo diagnoses. CLL/SLL and AITL were admixed in the same lymph nodes (3/3 cases) and in the bone marrow (1/2 cases). In all cases, the AITL comprised prominent clear cells with a strong T follicular ...
British Journal of Cancer, 2018
BACKGROUND: Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal di... more BACKGROUND: Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels. METHODS: In this multi-institutional study, we first examined the histological features displayed by each collected tumour (n = 74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed. RESULTS: Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/ transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligandreceptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa. CONCLUSIONS: Taken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits.
The British Journal of Radiology, 2016
Treating metastatic colorectal cancer with anti-EGFR monoclonal antibodies is recommended only fo... more Treating metastatic colorectal cancer with anti-EGFR monoclonal antibodies is recommended only for patients whose tumour does not harbour mutations of KRAS or NRAS. The aim of this study was to investigate the biology of rectal cancers and specifically to evaluate the relationship between fluorine-18 fludeoxyglucose (18 F-FDG) positron emission tomography (PET) intensity and heterogeneity parameters and their mutational status. Methods: 151 patients with newly diagnosed rectal cancer were included in this retrospective study. All patients underwent a baseline 18 F-FDG PET/CT within a median time interval of 27 days of tumour tissue sampling, which was performed before any treatment. Standardized uptake values (SUVs), volume-based parameters and texture analysis were studied. We retrospectively performed KRAS genotyping on codons 12, 13, 61, 117 and 146, NRAS genotyping on codons 12, 13 and 61 and BRAF on codon 600. Associations between PET/CT parameters and the mutational status were assessed using univariate and multivariate analysis. Results: 83 (55%) patients had an RAS mutation: 74 KRAS and 9 NRAS, while 68 patients had no mutation (wild-type tumours). No patient had BRAF mutation. First-order features based on intensity histogram analysis were significantly associated with RAS mutations: maximum SUV (SUV max) (p-value 5 0.002), mean SUV (p-value 5 0.006), skewness (p-value 5 0.049), SUV standard deviation (p-value 5 0.001) and SUV coefficient of variation (SUV cov) (p-value 5 0.001). Both SUV cov and SUV max showed an area under the curve of 0.65 with sensitivity of 56% and 69%, respectively, and specificity of 64% and 52%, respectively. None of the volume-based (metabolic tumour volume and total lesion glycolysis), nor local or regional textural features were associated with the presence of RAS mutations. Conclusion: Although rectal cancers with KRAS or NRAS mutations display a significantly higher glucose metabolism than wild-type cancers, the accuracy of the currently proposed quantitative metrics extracted from 18 F-FDG PET/CT is not sufficiently high for playing a meaningful clinical role. Advances in knowledge: RAS-mutated rectal cancers have a significantly higher glucose metabolism. However, the accuracy of 18 F-FDG PET/CT quantitative metrics is not as such as the technique could play a clinical role.
Bone Marrow Transplantation, 1999
Intensification using peripheral blood stem cells collected after chemotherapy followed by growth... more Intensification using peripheral blood stem cells collected after chemotherapy followed by growth factors is being increasingly investigated as an alternative to conventional chemotherapy for mantle cell non-Hodgkin lymphoma. We investigated 14 grades III-IV, t(11;14)-positive cases for contamination of PBSC collected after a polychemotherapy regimen followed by G-CSF. Patients were first treated with a polychemotherapy regimen. There were four CR, seven PR, two refractory and one early death. Seven patients have been transplanted, in whom PBSC were mobilized, using either cyclophosphamide/VP16 or Dexa-BEAM followed by G-CSF. For all patients, whether actually autografted or not, PB cells were tested at the time of regeneration on G-CSF after the first polychemotherapy or after the mobilizing regimen. PCR evaluation of contamination was performed first by a semi-quantitative approach, using serial dilutions of initial DNA, then confirmed using a limiting-dilution analysis. Two patients were not informative (one early death and one without an available molecular marker). PB cells collected at regeneration contained at least one log more lymphoma cells than steady-state blood or marrow, apart from in two cases. Moreover, where a mobilizing treatment diminished tumor burden in the patient, at the same time it increased PB contamination in most cases. We conclude that advanced mantle cell NHL appears to be largely resistant to significant in vivo purging by conventional chemotherapy. Where treatment brings benefits by reducing tumor load, it may at the same time negate it by mobilizing malignant cells into the collections used to intensify. Although the clonogenic potential of this massive infiltration is unknown (only gene marking studies could provide a definitive answer regarding the source of relapses), strategies aimed at reducing the level of contamination in the graft should be considered when designing future protocols.
Del 52pb Fragment Analysis ET carrying both CALR and JAK2-V617F mutations JAK2-V617F can coexisti... more Del 52pb Fragment Analysis ET carrying both CALR and JAK2-V617F mutations JAK2-V617F can coexisting with CALR mutations in rare ET/PMF cases ( McGaffin G. et al, 2014; Lim K.H. et al, 2015) The majority of PV carries a JAK2-V617F mutation (JAK2V617F). The recently described calreticulin (CALR) mutations are preferentially associated with JAK2-V617F-negative and Myeloproliferative Leukemia Virus Oncogene (MPL) mutations negative ET or PMF. (Cross N.C., 2011).
Clinical Medical Reviews and Case Reports, 2017
Revue médicale de Liège
Recent advances in medical genomics open new perspectives for personalized medicine through the i... more Recent advances in medical genomics open new perspectives for personalized medicine through the identification of genetic variants that influence drug response and/or the risk of side effects. Today, the clinical applications of pharmacogenetics remain scarce as a consequence of the cost and turn-around-time of genetic tests. However, a few tests are recommended, for instance before the prescription of some anti-cancer agents or the anti-retroviral agent abacavir. In the future, we will probably move either towards rapid targeted tests or towards a large screening, before any diagnosis, of all the genetic factors influencing the therapeutic response. In that case, physicians will have to consult the patient genomic data before drug prescription in order to personalize the choice of the therapeutic agent or its dosage. However, such a genomic approach brings economical and ethical questions and will require further progress in our capacity to interpret and store the personal genomic ...
Blood, 2007
Cyclin D1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpressi... more Cyclin D1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpression Virtually all cases of mantle cell lymphoma (MCL) carry the t(11;14)(q13;q32) translocation, leading to the juxtaposition of the CCND1/CYCLIND1 gene to the immunoglobulin heavy chain (IGH) joining region, resulting in cyclin D1 mRNA and protein overexpression. 1-3 The existence of "true" MCL negative for cyclin D1 has been controversial but was recently substantiated by gene expression profiling. 4 Fu et al reported 6 cases of cyclin D1negative lymphomas with pathologic and clinical features otherwise typical of MCL, and a molecular signature similar to that of cyclin D1-positive MCL. In these cyclin D1-negative MCL, the tumor cells overexpressed instead either cyclin D2 or cyclin D3, but had no evidence of chromosomal aberration involving the corresponding CCND2 and CCND3 genetic loci. Subsequently,
European Journal of Pediatrics, 2013
Transient neonatal leukemia occurs almost exclusively in Down syndrome babies. We report here the... more Transient neonatal leukemia occurs almost exclusively in Down syndrome babies. We report here the unusual case of a newborn without Down syndrome who presented neonatal transient leukemia and who achieved spontaneously complete remission. Trisomy 21 and GATA1 mutation were both present in leukemic cells. While close follow-up is advised since true leukemia may develop later, the patient is still in remission for 2.5 years. We performed a literature review of 15 other similar cases. Our case of transient leukemia without Down syndrome and the literature review highlight the important role of trisomy 21 and GATA1 mutation in the development of transient neonatal leukemia.
Acta Clinica Belgica, 2007
RNA-Seq allows for a rapid screening of fusion transcripts and can identifiy the rare ones, for w... more RNA-Seq allows for a rapid screening of fusion transcripts and can identifiy the rare ones, for which no diagnostic test is developed for routine work. In addition to the « transcriptome » information, we used the « genome » information present in the data to identify the chromosomal breakpoints. This methodology was more time-efficient than performing a screening by PCR, and more cost-efficient than performing a whole genome sequencing. We received a bone marrow from a 77-year old patient presenting with hypereosinophilia. FIP1L1-PDGFRA fusion was not detected, but cytogenetic analysis revealed a t(1;5)(q21;q33), with locus 5q33 corresponding to PDGFRB. This was in accordance with a diagnosis of Chronic Eosinophilic Leukemia (CEL), a rare subtype of myeloproliferative neoplasm, frequently characterized by rearrangements involving PDGFRA/B or FGFR1 genes. As FISH couldn’t identify the fusion partner of PDGFRB, we performed a whole transcriptome sequencing (or RNA-Seq). Introduction
British Journal of Haematology, 2011
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
The American Journal of Surgical Pathology, Jan 11, 2021
Cells
Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Gemcitabine is th... more Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor prognosis. Gemcitabine is the first-line therapy for PDAC, but gemcitabine resistance is a major impediment to achieving satisfactory clinical outcomes. This study investigated whether methylglyoxal (MG), an oncometabolite spontaneously formed as a by-product of glycolysis, notably favors PDAC resistance to gemcitabine. We observed that human PDAC tumors expressing elevated levels of glycolytic enzymes together with high levels of glyoxalase 1 (GLO1), the major MG-detoxifying enzyme, present with a poor prognosis. Next, we showed that glycolysis and subsequent MG stress are triggered in PDAC cells rendered resistant to gemcitabine when compared with parental cells. In fact, acquired resistance, following short and long-term gemcitabine challenges, correlated with the upregulation of GLUT1, LDHA, GLO1, and the accumulation of MG protein adducts. We showed that MG-mediated activation of heat shock response is, at lea...
European Journal of Haematology, 2013
To the Editor: Refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T) is a rare en... more To the Editor: Refractory anaemia with ring sideroblasts and thrombocytosis (RARS-T) is a rare entity and is defined as an overlap syndrome with clinical and morphologic features of both myelodysplastic syndrome (MDS) and BCR-ABL-negative myeloproliferative neoplasm, including marked thrombocytosis associated with abnormal megakaryocytes (1). Mutations in the Janus Kinase 2 gene (JAK2) and/or Splicing Factor 3B subunit 1 (SF3B1) gene have been detected in 50-70% of patients with RARS-T (2-4). The presence of such a mutation in either JAK2 or SF3B1 was associated with a better overall survival in a recent European study (5). Because of its activity in lower-risk MDS with or without the 5q-cytogenetic abnormality (6) and in myelofibrosis (7), lenalidomide treatment has been given with success in two patients with RARS-T. In this letter, we would like to report a case of RARS-T that was successfully treated by lenalidomide. An 84-years-old woman was referred for unexplained normocytic anaemia (Hb 7.7 g/dL) with marked thrombocytosis
American Journal of Surgical Pathology, 2021
Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an indolent small B-cell neo... more Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is an indolent small B-cell neoplasm that may transform into a clinically aggressive disease, namely Richter syndrome, usually as diffuse large B-cell lymphoma. Besides, CLL/SLL encompasses an increased risk of developing other secondary cancers, including a variety of T-cell lymphomas, often of the anaplastic large-cell type or with a cytotoxic phenotype. Here, we report a small series of patients with composite lymphomas consisting of CLL/SLL and angioimmunoblastic T-cell lymphoma (AITL), a hitherto unrecognized association. The 3 patients (1 male/2 females, 68 to 83 y) presented with high-grade-type symptoms. One patient was clinically suspicious for Richter syndrome, in the others CLL/SLL and AITL were concomitant de novo diagnoses. CLL/SLL and AITL were admixed in the same lymph nodes (3/3 cases) and in the bone marrow (1/2 cases). In all cases, the AITL comprised prominent clear cells with a strong T follicular ...
British Journal of Cancer, 2018
BACKGROUND: Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal di... more BACKGROUND: Primary adenocarcinoma of the anal canal is a rare and aggressive gastrointestinal disease with unclear pathogenesis. Because of its rarity, no clear clinical practice guideline has been defined and a targeted therapeutic armamentarium has yet to be developed. The present article aimed at addressing this information gap by in-depth characterising the anal glandular neoplasms at the histologic, immunologic, genomic and epidemiologic levels. METHODS: In this multi-institutional study, we first examined the histological features displayed by each collected tumour (n = 74) and analysed their etiological relationship with human papillomavirus (HPV) infection. The intratumoural immune cell subsets (CD4, CD8, Foxp3), the expression of immune checkpoints (PD-1, PD-L1), the defect in mismatch repair proteins and the mutation analysis of multiple clinically relevant genes in the gastrointestinal cancer setting were also determined. Finally, the prognostic significance of each clinicopathological variable was assessed. RESULTS: Phenotypic analysis revealed two region-specific subtypes of anal canal adenocarcinoma. The significant differences in the HPV status, density of tumour-infiltrating lymphocytes, expression of immune checkpoints and mutational profile of several targetable genes further supported the separation of these latter neoplasms into two distinct entities. Importantly, anal gland/ transitional-type cancers, which poorly respond to standard treatments, displayed less mutations in downstream effectors of the EGFR signalling pathway (i.e., KRAS and NRAS) and demonstrated a significantly higher expression of the immune inhibitory ligandreceptor pair PD-1/PD-L1 compared to their counterparts arising from the colorectal mucosa. CONCLUSIONS: Taken together, the findings reported in the present article reveal, for the first time, that glandular neoplasms of the anal canal arise by HPV-dependent or independent pathways. These etiological differences leads to both individual immune profiles and mutational landscapes that can be targeted for therapeutic benefits.
The British Journal of Radiology, 2016
Treating metastatic colorectal cancer with anti-EGFR monoclonal antibodies is recommended only fo... more Treating metastatic colorectal cancer with anti-EGFR monoclonal antibodies is recommended only for patients whose tumour does not harbour mutations of KRAS or NRAS. The aim of this study was to investigate the biology of rectal cancers and specifically to evaluate the relationship between fluorine-18 fludeoxyglucose (18 F-FDG) positron emission tomography (PET) intensity and heterogeneity parameters and their mutational status. Methods: 151 patients with newly diagnosed rectal cancer were included in this retrospective study. All patients underwent a baseline 18 F-FDG PET/CT within a median time interval of 27 days of tumour tissue sampling, which was performed before any treatment. Standardized uptake values (SUVs), volume-based parameters and texture analysis were studied. We retrospectively performed KRAS genotyping on codons 12, 13, 61, 117 and 146, NRAS genotyping on codons 12, 13 and 61 and BRAF on codon 600. Associations between PET/CT parameters and the mutational status were assessed using univariate and multivariate analysis. Results: 83 (55%) patients had an RAS mutation: 74 KRAS and 9 NRAS, while 68 patients had no mutation (wild-type tumours). No patient had BRAF mutation. First-order features based on intensity histogram analysis were significantly associated with RAS mutations: maximum SUV (SUV max) (p-value 5 0.002), mean SUV (p-value 5 0.006), skewness (p-value 5 0.049), SUV standard deviation (p-value 5 0.001) and SUV coefficient of variation (SUV cov) (p-value 5 0.001). Both SUV cov and SUV max showed an area under the curve of 0.65 with sensitivity of 56% and 69%, respectively, and specificity of 64% and 52%, respectively. None of the volume-based (metabolic tumour volume and total lesion glycolysis), nor local or regional textural features were associated with the presence of RAS mutations. Conclusion: Although rectal cancers with KRAS or NRAS mutations display a significantly higher glucose metabolism than wild-type cancers, the accuracy of the currently proposed quantitative metrics extracted from 18 F-FDG PET/CT is not sufficiently high for playing a meaningful clinical role. Advances in knowledge: RAS-mutated rectal cancers have a significantly higher glucose metabolism. However, the accuracy of 18 F-FDG PET/CT quantitative metrics is not as such as the technique could play a clinical role.
Bone Marrow Transplantation, 1999
Intensification using peripheral blood stem cells collected after chemotherapy followed by growth... more Intensification using peripheral blood stem cells collected after chemotherapy followed by growth factors is being increasingly investigated as an alternative to conventional chemotherapy for mantle cell non-Hodgkin lymphoma. We investigated 14 grades III-IV, t(11;14)-positive cases for contamination of PBSC collected after a polychemotherapy regimen followed by G-CSF. Patients were first treated with a polychemotherapy regimen. There were four CR, seven PR, two refractory and one early death. Seven patients have been transplanted, in whom PBSC were mobilized, using either cyclophosphamide/VP16 or Dexa-BEAM followed by G-CSF. For all patients, whether actually autografted or not, PB cells were tested at the time of regeneration on G-CSF after the first polychemotherapy or after the mobilizing regimen. PCR evaluation of contamination was performed first by a semi-quantitative approach, using serial dilutions of initial DNA, then confirmed using a limiting-dilution analysis. Two patients were not informative (one early death and one without an available molecular marker). PB cells collected at regeneration contained at least one log more lymphoma cells than steady-state blood or marrow, apart from in two cases. Moreover, where a mobilizing treatment diminished tumor burden in the patient, at the same time it increased PB contamination in most cases. We conclude that advanced mantle cell NHL appears to be largely resistant to significant in vivo purging by conventional chemotherapy. Where treatment brings benefits by reducing tumor load, it may at the same time negate it by mobilizing malignant cells into the collections used to intensify. Although the clonogenic potential of this massive infiltration is unknown (only gene marking studies could provide a definitive answer regarding the source of relapses), strategies aimed at reducing the level of contamination in the graft should be considered when designing future protocols.
Del 52pb Fragment Analysis ET carrying both CALR and JAK2-V617F mutations JAK2-V617F can coexisti... more Del 52pb Fragment Analysis ET carrying both CALR and JAK2-V617F mutations JAK2-V617F can coexisting with CALR mutations in rare ET/PMF cases ( McGaffin G. et al, 2014; Lim K.H. et al, 2015) The majority of PV carries a JAK2-V617F mutation (JAK2V617F). The recently described calreticulin (CALR) mutations are preferentially associated with JAK2-V617F-negative and Myeloproliferative Leukemia Virus Oncogene (MPL) mutations negative ET or PMF. (Cross N.C., 2011).
Clinical Medical Reviews and Case Reports, 2017
Revue médicale de Liège
Recent advances in medical genomics open new perspectives for personalized medicine through the i... more Recent advances in medical genomics open new perspectives for personalized medicine through the identification of genetic variants that influence drug response and/or the risk of side effects. Today, the clinical applications of pharmacogenetics remain scarce as a consequence of the cost and turn-around-time of genetic tests. However, a few tests are recommended, for instance before the prescription of some anti-cancer agents or the anti-retroviral agent abacavir. In the future, we will probably move either towards rapid targeted tests or towards a large screening, before any diagnosis, of all the genetic factors influencing the therapeutic response. In that case, physicians will have to consult the patient genomic data before drug prescription in order to personalize the choice of the therapeutic agent or its dosage. However, such a genomic approach brings economical and ethical questions and will require further progress in our capacity to interpret and store the personal genomic ...
Blood, 2007
Cyclin D1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpressi... more Cyclin D1-negative mantle cell lymphoma with cryptic t(12;14)(p13;q32) and cyclin D2 overexpression Virtually all cases of mantle cell lymphoma (MCL) carry the t(11;14)(q13;q32) translocation, leading to the juxtaposition of the CCND1/CYCLIND1 gene to the immunoglobulin heavy chain (IGH) joining region, resulting in cyclin D1 mRNA and protein overexpression. 1-3 The existence of "true" MCL negative for cyclin D1 has been controversial but was recently substantiated by gene expression profiling. 4 Fu et al reported 6 cases of cyclin D1negative lymphomas with pathologic and clinical features otherwise typical of MCL, and a molecular signature similar to that of cyclin D1-positive MCL. In these cyclin D1-negative MCL, the tumor cells overexpressed instead either cyclin D2 or cyclin D3, but had no evidence of chromosomal aberration involving the corresponding CCND2 and CCND3 genetic loci. Subsequently,
European Journal of Pediatrics, 2013
Transient neonatal leukemia occurs almost exclusively in Down syndrome babies. We report here the... more Transient neonatal leukemia occurs almost exclusively in Down syndrome babies. We report here the unusual case of a newborn without Down syndrome who presented neonatal transient leukemia and who achieved spontaneously complete remission. Trisomy 21 and GATA1 mutation were both present in leukemic cells. While close follow-up is advised since true leukemia may develop later, the patient is still in remission for 2.5 years. We performed a literature review of 15 other similar cases. Our case of transient leukemia without Down syndrome and the literature review highlight the important role of trisomy 21 and GATA1 mutation in the development of transient neonatal leukemia.
Acta Clinica Belgica, 2007
RNA-Seq allows for a rapid screening of fusion transcripts and can identifiy the rare ones, for w... more RNA-Seq allows for a rapid screening of fusion transcripts and can identifiy the rare ones, for which no diagnostic test is developed for routine work. In addition to the « transcriptome » information, we used the « genome » information present in the data to identify the chromosomal breakpoints. This methodology was more time-efficient than performing a screening by PCR, and more cost-efficient than performing a whole genome sequencing. We received a bone marrow from a 77-year old patient presenting with hypereosinophilia. FIP1L1-PDGFRA fusion was not detected, but cytogenetic analysis revealed a t(1;5)(q21;q33), with locus 5q33 corresponding to PDGFRB. This was in accordance with a diagnosis of Chronic Eosinophilic Leukemia (CEL), a rare subtype of myeloproliferative neoplasm, frequently characterized by rearrangements involving PDGFRA/B or FGFR1 genes. As FISH couldn’t identify the fusion partner of PDGFRB, we performed a whole transcriptome sequencing (or RNA-Seq). Introduction
British Journal of Haematology, 2011
HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific re... more HAL is a multidisciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.