Christine Chomienne | Université Paris 7- Diderot (original) (raw)

Papers by Christine Chomienne

Journal of Clinical Oncology, Jun 15, 2003

Purpose: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patien... more Purpose: Arsenic trioxide (ATO) is capable of inducing a high hematologic response rate in patients with relapsed acute promyelocytic leukemia (APL). Preclinical observations have indicated that all-trans-retinoic acid (ATRA) may strongly enhance the response to ATO. Patients and Methods: Between 1998 and 2001, we conducted a randomized study of ATO alone versus ATO plus ATRA in 20 patients with relapsed APL, all previously treated with ATRA-containing chemotherapy. The primary objective was to demonstrate a significant reduction in the time necessary to obtain a complete remission (CR) in the ATO/ATRA group compared with the ATO group. Secondary objectives were safety and molecular response. Results: The CR rate after one ATO with or without ATRA induction cycle was 80%. Clinical and pharmacokinetic observations indicated that the main mechanism of action of ATO in vivo was the induction of APL cell differentiation. Hematologic and molecular response, time necessary to reach CR, and outcome were comparable in both treatment groups. Of 16 CR patients, three patients who reached a molecular remission after one induction cycle had all received chemotherapy for a treatment-induced hyperleukocytosis. Three additional patients who received further additional ATO with or without ATRA cycles converted later to molecular negativity. Conclusion: ATRA did not seem to significantly improve the response to ATO in patients relapsing from APL. Other potential combinations, including ATO plus chemotherapy, have to be tested.

The EMBO Journal, 1994

Communicated by P.Tiollais Nuclear bodies (NBs) are ultrastructurally defined granules predominan... more Communicated by P.Tiollais Nuclear bodies (NBs) are ultrastructurally defined granules predominantly found in dividing cells. Here we show that PML, a protein involved in the t(15;17) translocation of acute promyelocytic leukaemia (APL), is specifically bound to a NB. PML and several NBassociated proteins, found as auto-antigens in primary biliary cirrhosis (PBC), are co-localized and co-regulated. The APL-derived PML-RARa fusion protein is shown to be predominantly localized in the cytoplasm, whereas a fraction is nuclear and delocalizes the NB antigens to multiple smaller nuclear clusters devoid of ultrastructural organization. RA administration (which in APL patients induces blast differentiation and consequently complete remissions) causes the re-aggregation of PML and PBC auto-antigens onto the NB, while PML-RARa remains mainly cytoplasmic. Thus, PML-RARa expression leads to a RA-reversible alteration of a nuclear domain. These results shed a new light on the pathogenesis of APL and provide a molecular link between NBs and oncogenesis.

Blood cancer journal, Jan 11, 2015

Leukemia, 2004

We analyzed the outcome of patients aged more than 60 included in a multicenter trial in newly di... more We analyzed the outcome of patients aged more than 60 included in a multicenter trial in newly diagnosed acute promyelocytic leukemia (APL93 trial), which tested the role of early addition of chemotherapy to all trans retinoic acid (ATRA) and of maintenance with ATRA and/or low-dose chemotherapy. In total, 129/533 (24.2%) patients included in this trial were older than 60. The CR rate was 86% in patients older than 60 as compared to 94.5% in younger patients (P ¼ 0.0014), due to a higher incidence of early deaths in elderly patients. The 4-year incidence of relapse was 15.6% in adults older than 60 and 23.2% in younger adults although most elderly patients received less intensive consolidation chemotherapy. However, 18.6% of the patients older than 60 years who achieved CR died in CR, mainly from sepsis during consolidation course or maintenance treatment, as compared to 5.7% of younger adults (Po0.001). Thus, overall 4-year survival of elderly patients was 57.8% as compared to 78% in younger adults (Po0.0001). APL in elderly patients appears as sensitive to ATRA-Chemotherapy based regimen as in younger adults. Less favorable outcome is mainly due to an increase of early deaths and to toxicity of consolidation treatment, strongly suggesting a beneficial role for less intensive consolidation chemotherapy and possibly introduction of arsenic derivates in the treatment of APL in the elderly.

Journal of Clinical Oncology, 2004

Purpose To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemot... more Purpose To determine the results of treatment combining all-trans-retinoic acid (ATRA) and chemotherapy (CT) in childhood acute promyelocytic leukemia (APL). Patients and Methods Children (< 18 years) with newly diagnosed APL were included in the APL93 trial, treated by ATRA followed or combined with daunorubicin-cytarabine, and then randomly assigned between no maintenance, intermittent ATRA, continuous CT, or both. Results Of the 576 patients included in APL93 trial, 31 (5%) were children, including 22 girls (71%) and nine boys (29%). Thirty of the children (97%) obtained complete remission (CR). ATRA syndrome occurred in four children (13%), who all achieved CR, and headaches occurred in 12 children (39%), with signs of pseudotumor cerebri in five children (16%). Seven patients (23%) relapsed. None of the eight patients who received both ATRA and CT for maintenance relapsed. All relapsing patients achieved a second CR. Twenty-two patients remained in first CR after 43+ to 96+ ...

Cancer Research, 2007

Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by inef... more Myelodysplastic syndromes (MDS) comprise a heterogeneous group of disorders characterized by ineffective hematopoiesis, with an increased propensity to develop acute myelogenous leukemia (AML). The molecular basis for MDS progression is unknown, but a key element in MDS disease progression is loss of chromosomal material (genomic instability). Using our two-step mouse model for myeloid leukemic disease progression involving overexpression of human mutant NRAS and BCL2 genes, we show that there is a stepwise increase in the frequency of DNA damage leading to an increased frequency of error-prone repair of double-strand breaks (DSB) by nonhomologous end-joining. There is a concomitant increase in reactive oxygen species (ROS) in these transgenic mice with disease progression. Importantly, RAC1, an essential component of the ROS-producing NADPH oxidase, is downstream of RAS, and we show that ROS production in NRAS/BCL2 mice is in part dependent on RAC1 activity. DNA damage and error-pr...

Blood, 2007

Background. Mutations in the RARα-region ligand binding domain (LBD) of PML-RARα were detected in... more Background. Mutations in the RARα-region ligand binding domain (LBD) of PML-RARα were detected in 30 – 40% of patients (pts) tested after first relapse from ATRA-chemotherapy (CT) regimens in 2 North American Phase III trials. However, no follow-up data were reported to assess whether this affected subsequent outcome. Methods. In the current study, 8 relapse pts were tested by previously-published techniques for PML-RARα LBD mutations after relapse from ATRA-CT regimens of the EAG. Treatment was according to the APL2000 protocol: randomization to induction with ATRA+DNR with AraC (arm-A) or no AraC (arm-B) followed by 2 consolidation courses with DNR with (A) or without (B) AraC and then 2 years maintenance with ATRA for 15 days every 3 months, as well as, 6MP and MTX (Ades, et al, J Clin Oncology24, 5703, 2006); 1 off-protocol (OP) pt was treated according to APL-93, which is similar to APL2000-A (Fenaux, et al, Blood94, 1192, 1999). Results. Patient Treatment Days to Relapse Days ...

International Journal of Environmental Research and Public Health, 2022

The potential for the use of real-world data (RWD) to generate real-world evidence (RWE) that can... more The potential for the use of real-world data (RWD) to generate real-world evidence (RWE) that can inform clinical decision-making and health policy is increasingly recognized, albeit with hesitancy in some circles. If used appropriately, the rapidly expanding wealth of health data could improve healthcare research, delivery of care, and patient outcomes. However, this depends on two key factors: (1) building structures that increase the confidence and willingness of European Union (EU) citizens to permit the collection and use of their data, and (2) development of EU health policy to support and shape data collection infrastructures, methodologies, transmission, and use. The great potential for use of RWE in healthcare improvement merits careful exploration of the drivers of, and challenges preventing, efficient RWD curation. Literature-based research was performed to identify relevant themes and discussion topics for two sets of expert panels, organized by the European Alliance for...

Anticancer research

The retinoids are a large group of compounds structurally related to vitamin A. Retinoids elicit ... more The retinoids are a large group of compounds structurally related to vitamin A. Retinoids elicit specific biological responses by binding to and activating nuclear receptors. Information about the metabolism and storage of vitamin A and retinoids, their plasma transport and uptake and the retinoid dose efficient on target cell had to be established because retinoic acid (RA), the natural acidic derivative of vitamin A (retinol), is likely to be a key factor during specific phases of embryonic development and maintenance of normal differentiated phenotypes in adult, so vitamin A is involved in the normal morphological differentiation of the visual system. RA appears an important agent since it induces in vitro leukemic cells from acute promyelocytic leukemia (APL) to differentiate into mature functional granulocytes which lose their self-renewal ability and die spontaneously. In vivo, APL patients treated with oral all-trans retinoic acid (all-trans RA) alone achieve complete remissi...

The Hematology Journal, 2000

Efficacy of differentiating agents requires that their specific cellular targets are still expres... more Efficacy of differentiating agents requires that their specific cellular targets are still expressed and functional in the leukemic cells. One hypothesis to target sensitive cells is to select leukemic clones which harbor disrupted transcription factors. CBFalpha and CBFbeta are core-binding proteins which have been identified as transcription regulators of hematopoietic genes and shown to be altered in numerous leukemias. In M2 AML, the t(8;21) translocation, CBFalpha (AML1) is altered and produced as the AML1-ETO fusion protein. The fusion protein blocks transcription and differentiation mediated by G-CSF. Interestingly, AML1-ETO leukemic cell lines are sensitive to numerous cytokines in vitro and can be induced to differentiate in the presence of G-CSF and PMA. As in the APL differentiation model, primary culture provides a useful tool for therapeutic screening of differentiation inducers, we analysed the in vitro sensitivity of 10 fresh M2 AML t(8;21) leukemic samples to G-CSF and the functionality of G-CSF intracellular pathways. In vitro data were compared with in vivo data from four patients treated with rhG-CSF at the dosage of 5 microg/kg/day i.v. for two to three weeks before the initiation of AML induction chemotherapy and immunophenotypic analysis performed weekly to monitor in vivo differentiation. In vitro, an increase in CD34+ cells expressing differentiation antigens (CD11b, CD13 or CD15) was noted along with a decrease of immature CD34+/differentiation antigen negative cells. After two weeks of a daily rhG-CSF administration in vivo, a significant, albeit transient, decrease of blast count was achieved, concomitant with an increase in differentiated leukemic cells suggesting that in vivo differentiation occurs. Fresh t(8;21) leukemic cells possess functional G-CSF signaling pathways as normal activity and kinetics of STAT1 and STAT3 binding was observed. Furthermore, differentiation induction leads to a subsequent degradation of the AML1-ETO oncoprotein. The data presented here supports the claim that G-CSF can induce in vitro and in vivo differentiation of M2 AML t(8;21) cells.

Onkologie, 1996

Summary The current treatment of acute promyelocytic leukemia (APL, also called AML3 subtype) is ... more Summary The current treatment of acute promyelocytic leukemia (APL, also called AML3 subtype) is focused on differentiating agents such as the vitamin A derivative all-trans retinoic acid (ATRA). This agent is a novel and very promising therapy for this disease that is characterized cytogenetically by a translocation t(15;17)(q21;q22) involving the α-retinoic acid on chromosome 17 and the PML gene on chromosome 15. Clinical trials have demonstrated that ATRA followed by or combined with conventional chemotherapy may be more beneficial than chemotherapy for inducing complete remission. Unfortunately, as a single agent ATRA does not appear to be able to maintain patients in remission (median 6 months) and when relapse occurs resistance to a second induction of ATRA therapy is observed in almost all cases. Recently, our laboratory investigated whether specific features of the AML3 cells at relapse could explain the in vivo resistance observed. We have demonstrated that AML3 patient cells (from 4 patients) at relapse show high levels of CRABP, a cytosolic retinoic acid binding protein, and this protein was not detected prior to ATRA therapy. Relapse-AML3 cells (n=12) showed reduced differentiation induction when compared with ‘virgin’-AML3 cells. Results from this study suggest that CRABP could modulate ATRA cellular concentrations reaching the nucleus. This induced, ATRA hypercatabolytic state should be monitored during consolidation therapy and at relapse, to detect ATRA resistance in AML3.

Molecular and Cellular Probes, 2013

Using an acute promyelocytic leukemia (APL) preclinical model, we show that oncogene-specific PCR... more Using an acute promyelocytic leukemia (APL) preclinical model, we show that oncogene-specific PCR (Polymerase Chain Reaction)-based assays allow to evaluate the efficacy of immunotherapy combining all-trans retinoic acid (ATRA) and a DNA-based vaccine targeting the promyelocytic leukemia-retinoic acid receptor alpha (PML-RARα) oncogene. Kaplan-Meier survival analysis according to the peripheral blood PML-RARα normalized copy number (NCN) clearly shows that ATRA + DNA-treated mice with an NCN lower than 10 (43%) formed the group with a highly significant (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) survival advantage. Furthermore, a PCR assay was used to assess various tissues and organs for the presence of PML-RARα-positive cells in long-term survivors (n = 15). As expected, the majority of mice (n = 10) had no measurable tissue level of PML-RARα. However, five mice showed a weak positive signal in both the brain and spleen (n = 2), in the brain only (n = 2) and in the spleen only (n = 1). Thus tracking the oncogene-positive cells in long-term survivors reveals for the first time that extramedullary PML-RARα-positive cell reservoirs such as the brain may persist and be involved in relapses.

Leukemia & Lymphoma, 2004

Acute myeloid leukemia (AML) is a clonal malignant disease characterized by an increasing number ... more Acute myeloid leukemia (AML) is a clonal malignant disease characterized by an increasing number of immature myeloid cells arrested at various stages of granulocytic and monocytic differentiation. The stage of the blockage defines distinct AML subtypes (AML1 to AML5 are the most frequent ones). There is increasing evidence that the malignant clone is maintained by rare AML stem cells endowed with self-renewal capacity, which through extensive proliferation coupled to partial differentiation, generate leukemic progenitors and blasts, of which the vast majority have limited proliferative capacity. Contrarily to chemotherapy alone, which is still unable to cure most AML patients, the differentiation therapy, which consists in releasing the differentiation blockage of leukemic blasts, has succeeded, when it is combined with chemotherapy, to greatly improve the survival of AML3 patients, using retinoic acid as differentiating agent. However, this molecule is ineffective in other AML subtypes, which are the most frequent. We have shown that specific monoclonal antibodies (mAbs, H90 and A3D8) directed to the CD44 cell surface antigen, that is strongly expressed on human AML blasts, are capable of triggering terminal differentiation of leukemic blasts in AML1 to AML5 subtypes. These results have raised the perspective of developing a CD44-targeted differentiation therapy in most AML cases. Interestingly, these anti-CD44 mAbs can also induce the differentiation of AML cell lines, inhibit their proliferation and, in some cases, induce their apoptotic death. These results suggest that H90 and/or A3D8 mAbs may be capable to inhibit the proliferation of leukemic progenitors, to promote the differentiation of the leukemic stem cells at the expense of their self-renewal, and, perhaps, to induce their apoptotic death, thereby contributing to decrease the size of the leukemic clone. The challenges of an anti-CD44 based differentiation therapy in AML, and its importance in relation to the new other therapies developed in this malignancy, are discussed in this review.

Leukemia, 2000

The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT... more The purpose of this study was to assess the safety and efficacy of stem cell transplantation (SCT) mainly autologous SCT as consolidation therapy in APL patients who relapsed and achieved a second complete remission (CR2). Fifty adult patients with a first relapsed APL, of whom 39 had been previously treated with ATRA, entered a multicenter trial of oral ATRA until complete remission (CR) achievement followed by timed sequential chemotherapy (EMA combining etoposide 200 mg/m 2 /day for 3 days, mitoxantrone 12 mg/m 2 /day for 3 days, and cytarabine 500 mg/m 2 /day for two sequences of 3 days). EMA was started either after CR achievement, or on day 1 of ATRA because of initial white blood cell (WBC) counts .5 × 10 9 /l, or rapidly added to ATRA in order to prevent ATRA syndrome because WBC count increased under ATRA. Forty-five patients (90%, 95% CI 78%-97%) were in CR after induction therapy. Five patients died from infection during aplasia following EMA chemotherapy. Eleven patients who achieved CR had a familial HLA-identical donor and were allografted. The median disease-free survival (DFS) of allografted patients was 8.2 months. The 34 other CR patients were scheduled for autologous peripheral blood (PB) SCT (intent-to-treat group). Actually, autologous transplantation was only carried out in 22 patients (65%) (17 PBSCT and five autologous bone marrow transplantation (BMT)). Reasons for not autografting were early relapse (three patients), severe toxicity of EMA chemotherapy (six patients), and refusal or failure of stem cell harvest (three patients). The 3-year DFS rate of patients actually autografted was 77%. Among the 17 autografted patients still in CR2, nine patients have already reached a longer CR2 than first CR (CR1). Results of detection of PML/RARα by RT-PCR after autologous transplantation show negative findings in eight of the nine patients tested. We conclude that (1) ATRA combined to EMA chemotherapy is effective in the treatment of relapsed APL; (2) allogeneic BMT may be too toxic after salvage treatment including EMA intensive chemotherapy; (3) clinical outcome of autografted patients and preliminary molecular results regarding detection of PML/RARα after autologous PBSCT are encouraging. Leukemia (2000) 14,

Leukemia, 2003

Treatment combining ATRA and chemotherapy (CT) has improved the outcome of APL patients, by compa... more Treatment combining ATRA and chemotherapy (CT) has improved the outcome of APL patients, by comparison with CT alone. ATRA syndrome is a life-threatening complication of ATRA treatment whose prophylaxis remains somewhat controversial. In APL93 trial, newly diagnosed APL patients р65 years and with initial WBC counts below 5000/mm 3 were randomized between ATRA until CR achievement followed by CT (ATRA → CT) and ATRA with early addition of CT, on day 3 of ATRA treatment (ATRA + CT). The incidence of ATRA syndrome in the ATRA → CT arm was 18% (22/122) as compared to 9.2% (17/184) in the ATRA + CT arm (P = 0.035). In the ATRA → CT arm, three (2.5%) patients died from ATRA syndrome, as compared to one (0.5%) in the ATRA + CT group. Early addition of chemotherapy to ATRA in newly diagnosed APL with low WBC counts significantly reduced the incidence of ATRA syndrome.

Leukemia, 2003

With improved treatment of acute promyelocytic leukemia (APL) by all trans retinoic acid (ATRA) c... more With improved treatment of acute promyelocytic leukemia (APL) by all trans retinoic acid (ATRA) combined to anthracycline-aracytin chemotherapy (CT), a larger number of those patients may be at risk of late complications. Recently, the Rome group reported five cases of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML, non-APL) occurring during the course of 77 APL patients (6.5%) in complete remission (CR). From 1991 to 1998, we treated 677 newly diagnosed cases of APL, and 617 of them achieved CR with ATRA combined to CT (n ¼ 579) or CT alone (n ¼ 38); 246 of them received subsequent maintenance CT with 6 mercaptopurine and methotrexate. With a median follow-up of 51 months, 6 patients (0.97%) developed MDS, 13-74 months after the diagnosis of APL. In all six cases, t(15;17) and PML-RARalpha rearrangement were absent at the time of MDS diagnosis, and karyotype mainly showed complex cytogenetic abnormalities involving chromosomes 5 and/or 7, typical of MDS observed after treatment with alkylating agents, although none of the six patients had received such agents for the treatment of APL. Our findings suggest that MDS can indeed be a long-term complication in APL, although probably at lower incidence than that previously reported.

Leukemia, 2005

Internal tandem duplications (ITDs) of the FLT3 gene have been observed in about 35% of APL cases... more Internal tandem duplications (ITDs) of the FLT3 gene have been observed in about 35% of APL cases. If FLT3-ITD is associated with a worse outcome in patients with acute myeloid leukemia (AML) in general, its prognostic value in acute promyelocytic leukemia (APL) is still a matter of debate. We investigated incidence, associated clinical features, and prognostic implication of FLT3-ITD, but also FLT3-D835 point mutation and N-Ras or K-Ras mutations in 119 APL patients, all prospectively enrolled in the two consecutive APL-93 and APL-2000 trials. Mutation incidences were 38, 20, and 4%, for FLT3-ITD, FLT3-D835, and Ras, respectively. The presence of FLT3-ITD was associated with high white blood cell count, high Sanz index, M3-variant subtype, and V/S PML-RARa isoforms. Complete remission (CR), induction death, and death in CR rates were not affected by FLT3 or Ras mutations, as well as cumulative incidence of relapse. However, a trend for a shorter overall survival (P ¼ 0.09) was observed in FLT3-ITD patients, because of a very poor postrelapse survival (P ¼ 0.02). This feature, which has been also reported in patients with AML in general, is suggestive of an underlying genetic instability in FLT3-ITD patients, leading to the acquisition of additional unknown badprognosis gene mutations at relapse.

Journal of Clinical Oncology, 2012

Purpose Acute promyelocytic leukemia (APL) is rare in children. All-trans-retinoic acid (ATRA) co... more Purpose Acute promyelocytic leukemia (APL) is rare in children. All-trans-retinoic acid (ATRA) combined with chemotherapy, the reference treatment of APL, is generally considered to produce similar results in children and adults. However, previously published childhood APL studies have generally analyzed all patients age < 18 years as a group, without further dividing according to age. Patients and Methods We compared disease characteristics and outcomes of children (age ≤ 12 years), adolescents (13 to 18 years), and adults (> 18 years) included in two multicenter APL clinical trials (APL 93 and 2000 trials). Results Of the 833 patients age ≤ 60 years included in the two trials, 26 (3%), 58 (7%), and 749 (90%) were children, adolescents, and adults, respectively. Children had significantly higher baseline WBC counts (P < .001). The complete remission (CR) rate (92%, 100%, and 94.5%, respectively) and 5-year cumulative incidence of relapse (CIR; 28%, 20%, and 23%, respective...

Journal of Biological Chemistry, 2002

Ligand-induced transcription activation of retinoic acid (RA) target genes by nuclear receptors (... more Ligand-induced transcription activation of retinoic acid (RA) target genes by nuclear receptors (retinoic acid (RAR) and retinoid X (RXR) receptors) depends on the recruitment of coactivators. We have previously demonstrated that the small 15-kDa cellular RA-binding protein II (CRABPII) is a coactivator present in the RAdependent nuclear complex. As identifying cell-specific partners of CRABPII might help to understand the novel control of RA signaling, we performed a yeast two-hybrid screen of a hematopoietic HL-60 cDNA library using human CRABPII as bait and have subsequently identified human cyclin D3 as a partner of CRABPII. Cyclin D3 interacted with CRABPII in a ligand-independent manner and equally bound RAR␣, but not RXR␣, and only in the presence of RA. We further show that cyclin D3 positively modulated RA-mediated transcription through CRABPII. Therefore, cyclin D3 may be part of a ternary complex with CRABPII and RAR. Finally, we show that cyclin D3 expression paralleled HL-60 differentiation and arrest of cell growth. These findings led us to speculate that control of cell proliferation during induction of differentiation may directly involve, at the transcriptional level, nuclear receptors, coactivators, and proteins of the cell cycle in a cell-and nuclear receptor-specific manner.

British Journal of Haematology, 2008

the patient maintains full donor chimaerism with normal blood counts and immune function. This pa... more the patient maintains full donor chimaerism with normal blood counts and immune function. This patient's transplant conditioning regimen was designed to limit exposure to agents that may cause adverse effects in children with chromosomal breakage syndromes. Use of alemtuzumab (CAMPATH-1H) and fludarabine provided the required immune suppression, while the lowest considerable dose of the alkylator melphalan was adequate to provide modest myeloablation and to ensure successful engraftment. To our knowledge, this is the first account of a reducedintensity HSCT from an unrelated donor in a patient with Seckel syndrome. One prior report described the use of a conventional transplant regimen in a Seckel syndrome patient (Esperou-Bourdeau et al, 1993). Reduced-intensity HSCT conditioning regimens have been successfully used in other bone marrow failure syndromes (Shenoy et al, 2005; Gruhn et al, 2007) and metabolic disorders (Hansen et al, 2007). Selecting an appropriate conditioning regimen for a child with Seckel syndrome is particularly challenging due to the heterogeneity of the disorder and the lack of prior reports to guide the choice. There is a high likelihood that Seckel syndrome patients will exhibit some degree of increased sensitivity to DNA damaging agents, even with normal mitomycin C or DEB chromosomal breakage studies. The preparative regimen that we selected, with emphasis on immune suppression and minimal use of DNA-damaging agents, is an attractive option for additional children with this disorder, in the absence of an available test to quantify increased sensitivity.

Journal of Clinical Oncology, Jun 15, 2003

The EMBO Journal, 1994

Blood cancer journal, Jan 11, 2015

Leukemia, 2004

Journal of Clinical Oncology, 2004

Cancer Research, 2007

Blood, 2007

International Journal of Environmental Research and Public Health, 2022

Anticancer research

The Hematology Journal, 2000

Onkologie, 1996

Molecular and Cellular Probes, 2013

Leukemia & Lymphoma, 2004

Leukemia, 2000

Leukemia, 2003

Leukemia, 2005

Journal of Clinical Oncology, 2012

Journal of Biological Chemistry, 2002

British Journal of Haematology, 2008