ArticleBlood advances2020
Cotargeting BCL-2 and MCL-1 in high-risk B-ALL.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- MicroRNAs as potential prognostic biomarkers in acute lymphoblastic leukemia: a systematic review, meta-analysis, and bioinformatics study.Systematic reviews · 2026Pooled it
- A genomic and epigenomic lens into the biology of acute lymphoblastic leukaemia.Nature reviews. Cancer · 2026Review
- BCL-2 and MCL1 co-inhibition enhances glucocorticoid therapy in preclinical models of infant KMT2A-rearranged acute lymphoblastic leukaemia.British journal of haematology · 2026Article
- Toward a chemotherapy and allo-HSCT free future: the evolution of treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia.Frontiers in immunology · 2026Review
- NSUN2 promotes leukemogenesis by ferritin heavy chain 1-mediated anti-ferroptosis and enhancing global protein synthesis in an mClinical epigenetics · 2025Article
- Antileukemia efficacy of the dual BCL2/BCL-XL inhibitor AZD0466 in acute lymphoblastic leukemia preclinical models.Blood advances · 2025Article
- LIPA-frogging blast phase chronic myeloid leukemia: hopping over resistance with lysosomal targeting.Haematologica · 2025Article
- A Phase 1 First-in-Human Study of the MCL-1 Inhibitor AZD5991 in Patients with Relapsed/Refractory Hematologic Malignancies.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Combination fedratinib and venetoclax has activity against human B-ALL with high FLT3 expression.bioRxiv : the preprint server for biology · 2024Article
- Combination of MCL-1 and BCL-2 inhibitors is a promising approach for a host-directed therapy for tuberculosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Identification of bicyclic compounds that act as dual inhibitors of Bcl-2 and Mcl-1.Molecular diversity · 2023Article
- Article
- BH3 mimetics in combination with nilotinib or ponatinib represent a promising therapeutic strategy in blast phase chronic myeloid leukemia.Cell death discovery · 2022Article
- The Emerging Role of Venetoclax-Based Treatments in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2022Review
- Effective tumor cell abrogation via Venetoclax-mediated BCL-2 inhibition in KMT2A-rearranged acute B-lymphoblastic leukemia.Cell death discovery · 2022Article
- SFPQ-ABL1 and BCR-ABL1 use different signaling networks to drive B-cell acute lymphoblastic leukemia.Blood advances · 2022Article
- Synergistic activity of combined inhibition of anti-apoptotic molecules in B-cell precursor ALL.Leukemia · 2022Article
- Genetic Biomarkers and Their Clinical Implications in B-Cell Acute Lymphoblastic Leukemia in Children.International journal of molecular sciences · 2022Review
- Potent, p53-independent induction of NOXA sensitizes MLL-rearranged B-cell acute lymphoblastic leukemia cells to venetoclax.Oncogene · 2022Article
- The manipulation of apoptosis for cancer therapy using BH3-mimetic drugs.Nature reviews. Cancer · 2022Review
Corrections and comments
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Authors and funding
26 authors at 10 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Improving survival outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL) remains a clinical challenge. Relapsed disease has a poor prognosis despite the use of tyrosine kinase inhibitors (TKIs) for Philadelphia chromosome positive (Ph+ ALL) cases and immunotherapeutic approaches, including blinatumomab and chimeric antigen receptor T cells. Targeting aberrant cell survival pathways with selective small molecule BH3-mimetic inhibitors of BCL-2 (venetoclax, S55746), BCL-XL (A1331852), or MCL1 (S63845) is an emerging therapeutic option. We report that combined targeting of BCL-2 and MCL1 is synergistic in B-ALL in vitro. The combination demonstrated greater efficacy than standard chemotherapeutics and TKIs in primary samples from adult B-ALL with Ph+ ALL, Ph-like ALL, and other B-ALL. Moreover, combined BCL-2 or MCL1 inhibition with dasatinib showed potent killing in primary Ph+ B-ALL cases, but the BH3-mimetic combination appeared superior in vitro in a variety of Ph-like ALL samples. In PDX models, combined BCL-2 and MCL1 targeting eradicated ALL from Ph- and Ph+ B-ALL cases, although fatal tumor lysis was observed in some instances of high tumor burden. We conclude that a dual BH3-mimetic approach is highly effective in diverse models of high-risk human B-ALL and warrants assessment in clinical trials that incorporate tumor lysis precautions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.