ORCID Profile
0000-0001-6626-5843
Current Organisations
KU Leuven
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VIB
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Publisher: American Association for Cancer Research (AACR)
Date: 23-09-2022
DOI: 10.1158/1078-0432.22476449
Abstract: Supplementary methods, tables, figure legends
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476449.V1
Abstract: Supplementary methods, tables, figure legends
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476428
Abstract: RNA-seq data
Publisher: Springer Science and Business Media LLC
Date: 20-11-2017
DOI: 10.1038/LEU.2017.328
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476443.V1
Abstract: Suppl. figure 1: Doxorubicin and vincristine are not synergistic with KPT-8602 in diminishing proliferation of B-ALL and T-ALL
Publisher: American Society of Hematology
Date: 25-01-2018
DOI: 10.1182/BLOOD-2017-07-797597
Abstract: One-third of T-ALL cases with JAK3 mutation harbor 2 JAK3 mutations. Double JAK3 mutants show stronger signaling than single JAK3 mutants.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476428.V1
Abstract: RNA-seq data
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 28-06-2018
Publisher: Springer Science and Business Media LLC
Date: 2012
DOI: 10.1038/NATURE10725
Publisher: American Society of Hematology
Date: 06-09-2019
Abstract: Suz12 inactivation cooperates with JAK3 mutant signaling to drive T-ALL development. JAK3/Suz12 mutant leukemia cells show increased sensitivity to PI3K/mTOR, VEGF receptor, and HSP90 inhibitors.
Publisher: American Association for Cancer Research (AACR)
Date: 30-04-2018
DOI: 10.1158/2159-8290.CD-17-0583
Abstract: Leukemia is caused by the accumulation of multiple genomic lesions in hematopoietic precursor cells. However, how these events cooperate during oncogenic transformation remains poorly understood. We studied the cooperation between activated JAK3/STAT5 signaling and HOXA9 overexpression, two events identified as significantly co-occurring in T-cell acute lymphoblastic leukemia. Expression of mutant JAK3 and HOXA9 led to a rapid development of leukemia originating from multipotent or lymphoid-committed progenitors, with a significant decrease in disease latency compared with JAK3 or HOXA9 alone. Integrated RNA sequencing, chromatin immunoprecipitation sequencing, and Assay for Transposase-Accessible Chromatin using sequencing (ATAC-seq) revealed that STAT5 and HOXA9 have co-occupancy across the genome, resulting in enhanced STAT5 transcriptional activity and ectopic activation of FOS/JUN (AP1). Our data suggest that oncogenic transcription factors such as HOXA9 provide a fertile ground for specific signaling pathways to thrive, explaining why JAK/STAT pathway mutations accumulate in HOXA9-expressing cells. Significance: The mechanism of oncogene cooperation in cancer development remains poorly characterized. In this study, we model the cooperation between activated JAK/STAT signaling and ectopic HOXA9 expression during T-cell leukemia development. We identify a direct cooperation between STAT5 and HOXA9 at the transcriptional level and identify PIM1 kinase as a possible drug target in mutant JAK/STAT/HOXA9-positive leukemia cases. Cancer Discov 8(5) 616–31. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 517
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476434.V1
Abstract: Suppl. figure 4: KPT-8602 single treatment or combined treatment with dexamethasone does not lead to nuclear accumulation of IKBα nor to effects on NFκB target genes
Publisher: Springer Science and Business Media LLC
Date: 08-03-2016
DOI: 10.1038/LEU.2016.62
Publisher: American Association for the Advancement of Science (AAAS)
Date: 29-05-2019
DOI: 10.1126/SCITRANSLMED.AAU6246
Abstract: Selective inhibition of γ-secretase complexes targets T-ALL without the dose-limiting side effects of complete γ-secretase inhibition.
Publisher: Elsevier BV
Date: 06-2015
DOI: 10.1016/J.CCELL.2015.05.011
Abstract: T cell acute lymphoblastic leukemia (T-ALL) is caused by mutations affecting cell survival, proliferation, and differentiation. In addition to requiring these mutations, Passaro and colleagues and Pitt and colleagues in this issue of Cancer Cell demonstrate that T-ALL initiating cells residing in bone marrow depend on the CXCR4/CXCL12 signaling axis for disease maintenance and progression.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476431
Abstract: ChIP-seq data for NR3C1 bound genes
Publisher: American Society of Hematology
Date: 11-11-2021
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476434
Abstract: Suppl. figure 4: KPT-8602 single treatment or combined treatment with dexamethasone does not lead to nuclear accumulation of IKBα nor to effects on NFκB target genes
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529397
Abstract: AbstractPurpose: KPT-8602 (Eltanexor) is a second-generation exportin-1 (XPO1) inhibitor with potent activity against acute lymphoblastic leukemia (ALL) in preclinical models and with minimal effects on normal cells. In this study, we evaluated whether KPT-8602 would synergize with dexamethasone, vincristine, or doxorubicin, three drugs currently used for the treatment of ALL. Experimental Design: First, we searched for the most synergistic combination of KPT-8602 with dexamethasone, vincristine, or doxorubicin i in vitro /i in both B-ALL and T-ALL cell lines using proliferation and apoptosis as a readout. Next, we validated this synergistic effect by treatment of clinically relevant B- and T-ALL patient-derived xenograft models i in vivo /i . Finally, we performed RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to determine the mechanism of synergy. Results: KPT-8602 showed strong synergism with dexamethasone on human B-ALL and T-ALL cell lines as well as i in vivo /i in three patient-derived ALL xenografts. Compared with single-drug treatment, the drug combination caused increased apoptosis and led to histone depletion. Mechanistically, integration of ChIP-seq and RNA-seq data revealed that addition of KPT-8602 to dexamethasone enhanced the activity of the glucocorticoid receptor (NR3C1) and led to increased inhibition of E2F-mediated transcription. We observed strong inhibition of E2F target genes related to cell cycle, DNA replication, and transcriptional regulation. Conclusions: Our preclinical study demonstrates that KPT-8602 enhances the effects of dexamethasone to inhibit B-ALL and T-ALL cells via NR3C1- and E2F-mediated transcriptional complexes, allowing to achieve increased dexamethasone effects for patients. /
Publisher: Springer Science and Business Media LLC
Date: 06-07-2021
DOI: 10.1038/S41467-021-24442-9
Abstract: Spi-1 Proto-Oncogene (SPI1) fusion genes are recurrently found in T-cell acute lymphoblastic leukemia (T-ALL) cases but are insufficient to drive leukemogenesis. Here we show that SPI1 fusions in combination with activating NRAS mutations drive an immature T-ALL in vivo using a conditional bone marrow transplant mouse model. Addition of the oncogenic fusion to the NRAS mutation also results in a higher leukemic stem cell frequency. Mechanistically, genetic deletion of the β-catenin binding domain within Transcription factor 7 ( TCF7)-SPI1 or use of a TCF/β-catenin interaction antagonist abolishes the oncogenic activity of the fusion. Targeting the TCF7-SPI1 fusion in vivo with a doxycycline-inducible knockdown results in increased differentiation. Moreover, both pharmacological and genetic inhibition lead to down-regulation of SPI1 targets. Together, our results reveal an ex le where TCF7-SPI1 leukemia is vulnerable to pharmacological targeting of the TCF/β-catenin interaction.
Publisher: American Association for Cancer Research (AACR)
Date: 11-2021
DOI: 10.1158/1078-0432.CCR-20-1315
Abstract: KPT-8602 (Eltanexor) is a second-generation exportin-1 (XPO1) inhibitor with potent activity against acute lymphoblastic leukemia (ALL) in preclinical models and with minimal effects on normal cells. In this study, we evaluated whether KPT-8602 would synergize with dexamethasone, vincristine, or doxorubicin, three drugs currently used for the treatment of ALL. First, we searched for the most synergistic combination of KPT-8602 with dexamethasone, vincristine, or doxorubicin in vitro in both B-ALL and T-ALL cell lines using proliferation and apoptosis as a readout. Next, we validated this synergistic effect by treatment of clinically relevant B- and T-ALL patient-derived xenograft models in vivo. Finally, we performed RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to determine the mechanism of synergy. KPT-8602 showed strong synergism with dexamethasone on human B-ALL and T-ALL cell lines as well as in vivo in three patient-derived ALL xenografts. Compared with single-drug treatment, the drug combination caused increased apoptosis and led to histone depletion. Mechanistically, integration of ChIP-seq and RNA-seq data revealed that addition of KPT-8602 to dexamethasone enhanced the activity of the glucocorticoid receptor (NR3C1) and led to increased inhibition of E2F-mediated transcription. We observed strong inhibition of E2F target genes related to cell cycle, DNA replication, and transcriptional regulation. Our preclinical study demonstrates that KPT-8602 enhances the effects of dexamethasone to inhibit B-ALL and T-ALL cells via NR3C1- and E2F-mediated transcriptional complexes, allowing to achieve increased dexamethasone effects for patients.
Publisher: Informa UK Limited
Date: 04-05-2018
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476437
Abstract: Suppl. figure 3: Dexamethasone and dexamethasone+KPT-8602 treatment induce NR3C1 binding and leads to differential gene expression of the bound genes in the SUP-T1 cell line
Publisher: Springer Science and Business Media LLC
Date: 25-08-2018
Publisher: American Society of Hematology
Date: 08-12-2016
DOI: 10.1182/BLOOD-2016-03-703454
Abstract: A subset of T-ALL cases show high expression of hedgehog pathway genes including the SHH ligand and the GLI1 transcription factor. T-ALL s les with high GLI1 expression levels respond to hedgehog inhibitor treatment in vitro and in vivo.
Publisher: Springer Science and Business Media LLC
Date: 19-09-2018
Publisher: Springer Science and Business Media LLC
Date: 30-08-2017
DOI: 10.1038/LEU.2017.276
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6529397.V1
Abstract: AbstractPurpose: KPT-8602 (Eltanexor) is a second-generation exportin-1 (XPO1) inhibitor with potent activity against acute lymphoblastic leukemia (ALL) in preclinical models and with minimal effects on normal cells. In this study, we evaluated whether KPT-8602 would synergize with dexamethasone, vincristine, or doxorubicin, three drugs currently used for the treatment of ALL. Experimental Design: First, we searched for the most synergistic combination of KPT-8602 with dexamethasone, vincristine, or doxorubicin i in vitro /i in both B-ALL and T-ALL cell lines using proliferation and apoptosis as a readout. Next, we validated this synergistic effect by treatment of clinically relevant B- and T-ALL patient-derived xenograft models i in vivo /i . Finally, we performed RNA-sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to determine the mechanism of synergy. Results: KPT-8602 showed strong synergism with dexamethasone on human B-ALL and T-ALL cell lines as well as i in vivo /i in three patient-derived ALL xenografts. Compared with single-drug treatment, the drug combination caused increased apoptosis and led to histone depletion. Mechanistically, integration of ChIP-seq and RNA-seq data revealed that addition of KPT-8602 to dexamethasone enhanced the activity of the glucocorticoid receptor (NR3C1) and led to increased inhibition of E2F-mediated transcription. We observed strong inhibition of E2F target genes related to cell cycle, DNA replication, and transcriptional regulation. Conclusions: Our preclinical study demonstrates that KPT-8602 enhances the effects of dexamethasone to inhibit B-ALL and T-ALL cells via NR3C1- and E2F-mediated transcriptional complexes, allowing to achieve increased dexamethasone effects for patients. /
Publisher: Ferrata Storti Foundation (Haematologica)
Date: 04-12-2018
Publisher: Springer Science and Business Media LLC
Date: 02-02-2023
Publisher: American Association for Cancer Research (AACR)
Date: 19-08-2015
DOI: 10.1158/1557-3265.HEMMAL14-B05
Abstract: Introduction: Combined activation of specific oncogenes is a general feature of human cancer and suggests that co-occurrence of particular oncogenic factors provides a selective advantage during cellular transformation. However, the exact molecular mechanisms by which oncoproteins cooperate during malignant transformation often remains elusive. Here, we study the functional relationship between the cooperative oncogenes NOTCH1 and TLX1 in the context of T-cell acute lymphoblastic leukemia to better understand their cooperative mechanism of action during T cell transformation. Methods: In this study, we performed chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) for the TLX1 homeobox oncoprotein in the T-ALL cell line ALL-SIL and analyzed the transcriptional response before and after TLX1 modulation using microarray based methods. We performed integration of TLX1 ChIPseq data with publically available transcription factor binding profiles in T-ALL and evaluated the immunophenotypic and transcriptional effects of ectopic TLX1 expression in thymus-derived CD34+ T-cell progenitors. Results: Integration of TLX1 ChIPseq data with gene expression profiles after TLX1 knockdown in the TLX1 positive T-ALL cell line ALL-SIL, confirmed the previously established role for TLX1 as transcriptional repressor in T-ALL biology. In line with previous reports (Della-Gatta et al., Nature Medicine, 2012), de novo TLX1 motif discovery identified RUNX1 and ETS1 as important mediators of the global TLX1 transcriptional network. Next, we used TLX1 ChIPseq data to define TLX1 bound super-enhancer including several loci critically involved in T-cell biology (e.g. T-cell receptor loci, RAG2, MYB). Furthermore, Gene set Enrichment Analysis (GSEA) showed that TLX1-defined super-enhancers were significantly affected by JQ1 treatment in ALL-SIL. Integration of our TLX1 ChIP-seq data with publically available ChIP-seq data for ICN1, RUNX1 and ETS1 in T-ALL cells (Wang et al., PNAS, 2013) showed a remarkable genome-wide overlap between the binding sites of these four transcription factors. Integration of these binding patterns with transcriptional read-out revealed an unprecedented transcriptional antagonism between TLX1 and NOTCH1, in which TLX1 suppresses the oncogenic NOTCH1 transcriptional program including IL7R, NOTCH3 and c-MYC. In line with this observation, ectopic TLX1 expression in CD34+ human thymic precursor T-cells broadly interfered with the normal T-cell differentiation program causing differentiation arrest, massive apoptosis and a significant downregulation of NOTCH1 target genes including reduced IL7R-alpha surface expression. Conclusion: In conclusion, our study reveals unexpected transcriptional antagonism between the cooperative oncogenes TLX1 and NOTCH1 in the biology of T-ALL. TLX1 mediated suppression of NOTCH signaling might be critically involved in the pre-leukemic phenotype (reduced thymus size and decreased cellularity) that has been observed in Lck-TLX1 transgenic mice (De Keersmaecker et al., Nature Medicine, 2010). Moreover, our results suggests that full malignant transformation of TLX1-driven leukemias might only be possible through acquisition of secondary NOTCH1 mutations that can overcome the initial TLX1 mediated suppression of NOTCH1 signaling, which is in line with the high frequency of gain-of-function NOTCH1 mutations in TLX1 positive human T-ALL. Citation Format: Kaat Durinck, Wouter Van Loocke, Joni Van der Meulen, Inge Van de Walle, Pieter Rondou, Charles E. De Bock, Bruce Poppe, Jan Cools, Jean Soulier, Tom Taghon, Frank Speleman, Pieter Van Vlierberghe. Transcriptional antagonism between the cooperative oncogenes TLX1 and NOTCH1 in T-cell acute lymphoblastic leukemia. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies Sep 20-23, 2014 Philadelphia, PA. Philadelphia (PA): AACR Clin Cancer Res 2015 (17 Suppl):Abstract nr B05.
Publisher: Wiley
Date: 07-08-2018
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476437.V1
Abstract: Suppl. figure 3: Dexamethasone and dexamethasone+KPT-8602 treatment induce NR3C1 binding and leads to differential gene expression of the bound genes in the SUP-T1 cell line
Publisher: Springer Science and Business Media LLC
Date: 25-06-2015
DOI: 10.1038/LEU.2015.162
Abstract: The TLX1 transcription factor is critically involved in the multi-step pathogenesis of T-cell acute lymphoblastic leukemia (T-ALL) and often cooperates with NOTCH1 activation during malignant T-cell transformation. However, the exact molecular mechanism by which these T-cell specific oncogenes cooperate during transformation remains to be established. Here, we used chromatin immunoprecipitation followed by sequencing to establish the genome-wide binding pattern of TLX1 in human T-ALL. This integrative genomics approach showed that ectopic TLX1 expression drives repression of T cell-specific enhancers and mediates an unexpected transcriptional antagonism with NOTCH1 at critical target genes, including IL7R and NOTCH3. These phenomena coordinately trigger a TLX1-driven pre-leukemic phenotype in human thymic precursor cells, reminiscent of the thymus regression observed in murine TLX1 tumor models, and create a strong genetic pressure for acquiring activating NOTCH1 mutations as a prerequisite for full leukemic transformation. In conclusion, our results uncover a functional antagonism between cooperative oncogenes during the earliest phases of tumor development and provide novel insights in the multi-step pathogenesis of TLX1-driven human leukemia.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476440.V1
Abstract: Suppl. figure 2: PDX s les have different basal NR3C1 expression levels.
Publisher: American Association for Cancer Research (AACR)
Date: 07-2019
DOI: 10.1158/1538-7445.AM2019-3696
Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease. The PHF6 gene is frequently targeted by loss-of-function mutations or deletions, with the highest prevalence in TLX1 or TLX3 rearranged T-ALLs. To gain insights into the putative function of PHF6 as a tumor suppressor in the T-cell lineage, we investigated the effects of PHF6 knock down during normal and malignant thymocytes. Notably, we observed broad effects on the investigated transcriptomes suggesting an important role for PHF6 in gene regulation. Furthermore, IL7R was identified as a common transcriptional target that was significantly upregulated upon PHF6 knockdown in both normal and malignant T cells. IL7R encodes a cytokine receptor critically involved in normal thymic development and which also acts as a bona fide oncogene in subset of primary T-ALLs. Thus, loss of PHF6 might further boost oncogenic addiction of leukemic T-cell lymphoblast to IL7-induced JAK-STAT signaling. To further explore the role of PHF6 inactivation in TLX1 driven leukemogenesis in vivo, we performed zebrafish modeling. For this, we generated a stable tg(rag2:TLX1, rag2:GFP) overexpressing as well as a phf6 knock out zebrafish line. These lines were crossed and offspring was monitored for T-ALL formation. Interestingly, three fish out of a cohort of 80 animals developed leukemia between 10 to 18 months of age. These leukemias originated from the thymus, spreaded throughout the whole body and were transplantable. Thus far, no leukemia was detected in PHF6 mutated or TLX1 overexpressing only zebrafish. Leukemic cells obtained from tumors that developed in the PHF6null TLX1rag2-TLX1/GFP animals were subjected to RNA-, ATAC- and H3K27ac ChIP-sequencing to assess the epigenetic status of the IL7R locus. In addition, exome-, and CNV-sequencing was performed to identify somatic lesions that cooperated loss of Phf6 during TLX1 driven T-cell transformation in zebrafish. Furthermore, additional injections of TLX1 in combination with an activating IL7R mutant into phf6 mutant zebrafish are currently ongoing to monitor additional effects on accelerated tumor formation. In conclusion, our data suggest that loss of PHF6 drives TLX1 mediated leukemogenesis, at least in part, by increasing surface IL7R expression. Therefore, we believe that increased addiction to oncogenic JAK-STAT signaling may render PHF6 mutant leukemic cells more sensitive to JAK inhibitors, a notion that we are currently investigating in our TLX1/PHF6 and TLX1/PHF6/IL7R zebrafish models. Citation Format: Siebe Loontiens, Kaat Durinck, Suzanne Vanhauwaert, Lisa Depestel, Mariana L. Oliveira, Givani Dewyn, Charles De Bock, João T. Barata, David Langenau, Jan Cools, Tom Taghon, Pieter Van Vlierberghe, Frank Speleman. PHF6loss drives IL7R oncogene addiction in TLX1 driven T-ALL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019 2019 Mar 29-Apr 3 Atlanta, GA. Philadelphia (PA): AACR Cancer Res 2019 (13 Suppl):Abstract nr 3696.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476431.V1
Abstract: ChIP-seq data for NR3C1 bound genes
Publisher: American Association for Cancer Research (AACR)
Date: 14-07-2015
DOI: 10.1158/1078-0432.CCR-14-2024
Abstract: Purpose: Activating ALK mutations are present in almost 10% of primary neuroblastomas and mark patients for treatment with small-molecule ALK inhibitors in clinical trials. However, recent studies have shown that multiple mechanisms drive resistance to these molecular therapies. We anticipated that detailed mapping of the oncogenic ALK-driven signaling in neuroblastoma can aid to identify potential fragile nodes as additional targets for combination therapies. Experimental Design: To achieve this goal, transcriptome profiling was performed in neuroblastoma cell lines with the ALKF1174L or ALKR1275Q hotspot mutations, ALK lification, or wild-type ALK following pharmacologic inhibition of ALK using four different compounds. Next, we performed cross-species genomic analyses to identify commonly transcriptionally perturbed genes in MYCN/ALKF1174L double transgenic versus MYCN transgenic mouse tumors as compared with the mutant ALK-driven transcriptome in human neuroblastomas. Results: A 77-gene ALK signature was established and successfully validated in primary neuroblastoma s les, in a neuroblastoma cell line with ALKF1174L and ALKR1275Q regulable overexpression constructs and in other ALKomas. In addition to the previously established PI3K/AKT/mTOR, MAPK/ERK, and MYC/MYCN signaling branches, we identified that mutant ALK drives a strong upregulation of MAPK negative feedback regulators and upregulates RET and RET-driven sympathetic neuronal markers of the cholinergic lineage. Conclusions: We provide important novel insights into the transcriptional consequences and the complexity of mutant ALK signaling in this aggressive pediatric tumor. The negative feedback loop of MAPK pathway inhibitors may affect novel ALK inhibition therapies, whereas mutant ALK induced RET signaling can offer novel opportunities for testing ALK-RET oriented molecular combination therapies. Clin Cancer Res 21(14) 3327–39. ©2015 AACR.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476440
Abstract: Suppl. figure 2: PDX s les have different basal NR3C1 expression levels.
Publisher: Springer Science and Business Media LLC
Date: 09-02-2016
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22476443
Abstract: Suppl. figure 1: Doxorubicin and vincristine are not synergistic with KPT-8602 in diminishing proliferation of B-ALL and T-ALL
Publisher: American Society of Hematology
Date: 11-12-2014
DOI: 10.1182/BLOOD-2014-05-574566
Abstract: High levels of the anti-apoptotic factor BCL-2 can be therapeutically exploited by the BH3 mimetic ABT-199 in human T-ALL.
No related grants have been discovered for Jan Cools.