Overcoming Venetoclax Resistance in CLL: A Novel BCL2/BCL-xL Dual-Efficacy Degrader Reshapes the Therapeutic Landscape丨EHA 2025

Overcoming Venetoclax Resistance in CLL: A Novel BCL2/BCL-xL Dual-Efficacy Degrader Reshapes the Therapeutic Landscape丨EHA 2025

In the high summer of 2025, the highly anticipated European Hematology Association (EHA) Annual Meeting was convened, bringing together top global experts in hematologic oncology to discuss cutting-edge progress and future directions in the field. In the Chronic Lymphocytic Leukemia (CLL) session, Dr. Daisy Diaz, a postdoctoral fellow from MD Anderson Cancer Center in the United States, representing the team of her mentor, Professor Deepa Sampath, delivered an exceptional presentation titled "A Study on Transcriptional Reprogramming and Survival Co-dependencies Following Venetoclax Resistance in Chronic Lymphocytic Leukemia." This research systematically unveiled the complex resistance mechanisms in CLL after the failure of Venetoclax treatment and proposed an innovative solution based on Proteolysis-Targeting Chimera (PROTAC) technology, offering a highly promising new approach for clinically overcoming dual-drug resistance.
BJH / JLB | Team of Professors Jianxiang Wang and Shaowei Qiu at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, Uncover Novel Mechanisms in t(8;21) AML and Identify Potential Therapeutic Targets

BJH / JLB | Team of Professors Jianxiang Wang and Shaowei Qiu at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, Uncover Novel Mechanisms in t(8;21) AML and Identify Potential Therapeutic Targets

Acute myeloid leukemia, subtype M2b (AML-M2b), was first identified in 1959 by Professor Chongli Yang at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences (CAMS), based on clinical features, bone marrow morphology, and cytology. He termed it “subacute granulocytic leukemia.” In 1973, Rowley and colleagues abroad reported the same leukemia subtype through cytogenetic methods. By the late 1990s, the team led by Professor Jianxiang Wang demonstrated that the chromosomal translocation t(8;21) leads to rearrangement of the AML1 and ETO genes, producing the AML1-ETO (RUNX1::RUNX1T1) fusion gene—the molecular hallmark of AML-M2b. This marker has since been widely applied in differential diagnosis and minimal residual disease (MRD) monitoring.
Blood Science Update | TREML2 Enhances Sensitivity of Acute Myeloid Leukemia Cells to Cytarabine via Suppression of the ERK Signaling Pathway

Blood Science Update | TREML2 Enhances Sensitivity of Acute Myeloid Leukemia Cells to Cytarabine via Suppression of the ERK Signaling Pathway

Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by clonal expansion of myeloid precursor cells. Cytarabine (Ara-C) remains a cornerstone of induction chemotherapy; however, primary and acquired resistance to Ara-C significantly limits its therapeutic efficacy. Emerging studies have suggested that immune checkpoint and receptor molecules may influence tumor chemosensitivity, yet the role of TREML2, a member of the TREM family, has remained largely unexplored in the AML context. This article, published in Blood Science, investigated TREML2 expression in AML and uncovered its role in modulating responsiveness to Ara-C.
Blood Science Update | Unexpected Poor Prognosis in ZNF618::NUTM1-Positive B-ALL: A Rare Case Defies Clinical Assumptions

Blood Science Update | Unexpected Poor Prognosis in ZNF618::NUTM1-Positive B-ALL: A Rare Case Defies Clinical Assumptions

ZNF618::NUTM1-rearranged B-cell lymphoblastic leukemia (B-ALL) is recognized as a rare but favorable subtype of pediatric leukemia. However, this new case report published in Blood Science challenges that prognostic certainty, documenting a 3-year-old patient whose disease proved resistant to conventional chemotherapy, multiple CAR-T therapies, and hematopoietic stem cell transplantation. The findings underscore the need to reassess expectations surrounding NUTM1 fusion-positive leukemias and investigate the biological complexity behind treatment failure.