LEUKEMIA白血病
LEUKEMIA(英文缩写 LEUKEMIA),ISSN 0887-6924,eISSN 1476-5551,中文译名:白血病 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
历年影响因子趋势
| JCR 数据年份 | 影响因子 | JCR 分区 |
|---|---|---|
| 2021 | 12.897 | Q1 |
| 2022 | 11.400 | Q1 |
| 2023 | 12.800 | Q1 |
| 2024 | 13.400 | Q1 |
| 2025 | 8.800 | Q1 |
LEUKEMIA 最新收录文献
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1. Alterations in 3D-DNA architecture drive unique leukemic profiles in IDH1- and DNMT3A-mutant acute myeloid leukemia.
PMID:日期:2026-10-01Acute myeloid leukemia (AML) is characterized by complex molecular alterations including mutations in epigenetic regulators such as IDH1 and DNMT3A, which are associated with globally altered DNA methylation affecting gene transcription, treatment choices, and outcomes. Additionally, IDH1 mutations are linked to changes in DNA-loop formation leading to oncogene upregulation. Here, we assessed 3D-DNA conformational changes in IDH1- and DNMT3A-mutated (mut) AML on a genome-wide scale as a global driver of leukemic signaling to identify novel therapeutic vulnerabilities. Using a cellular model with either IDH1 p.R132H or DNMT3A p.R882H mutation and primary AML samples, we analyzed mutation-specific 3D-DNA architecture by chromatin-conformation-capture (HiC) and transcriptional alterations by RNA sequencing. We identified both shared and distinct changes in compartmentalization and underlying DNA-loop formation in both DNMT3A- and IDH1-mut AML, which were linked to differential gene expression, supporting that 3D-genome architecture broadly influences transcription. Thereby, loop-mediated upregulation of IGF1R was identified in IDH1-mut AML, corresponding to specific sensitivity to IGF1R inhibitor BMS-754807 as mono- and combination therapy with ivosidenib, while DNMT3A-mut AML exhibited sensitivity to p38/MAPK inhibitor ralimetinib. Our data present a comprehensive map of global 3D-DNA alterations associated with IDH1- and DNMT3A mutations as a basis for further assessment of novel therapeutic strategies for both AML entities.
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3. Selective dependency of CALR-mutant myeloproliferative neoplasms on TYK2 signaling.
PMID:日期:2026-09-24Myeloproliferative neoplasms (MPN) are driven by the oncoproteins JAK2V617F, mutant calreticulin (CALR), and mutant thrombopoietin receptor (TPOR; MPL), all of which activate JAK/STAT signaling. While JAK2 signaling is engaged in all MPNs, TYK2 is dispensable for JAK2V617F-driven disease. Here, we hypothesized a distinct role for TYK2 in CALR-mutant driven MPN. We found constitutive TYK2 phosphorylation in CALRdel52/ins5- and MPLW515K- but not JAK2V617F-expressing cells. Structural modeling predicted similar TPOR-binding affinities for JAK2 and TYK2, while micropatterning experiments demonstrated that both JAK2WT and JAK2V617F displace TYK2 from the receptor. The TYK2 inhibitor deucravacitinib reduced viability and STAT3/5 phosphorylation in CALRdel52/ins5- and MPLW515K- but not JAK2V617F-mutant cells, with enhanced efficacy when combined with the JAK2-selective inhibitor fedratinib. Cellular response correlated with JAK2 protein abundance, as CALRins5 JAK2 clones outcompeted JAK2 clones upon TYK2 inhibition. In primary samples, deucravacitinib significantly suppressed colony growth in ET and PMF but not PV, and selectively reduced CALR- but not JAK2V617F-mutant allele burden. Similarly, CALR-mutant patient-specific iPSC-derived CD34 progenitors showed increased TYK2 phosphorylation and were more sensitive to TYK2 inhibition than their JAK2V617F counterparts. These findings identify TYK2 as a selective vulnerability in CALR-mutant MPN and support combined TYK2/JAK2 inhibition strategies to overcome JAK2-dependent resistance.
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4. Aberrant expression of MERTK activates BCR via CD79a in CLL cells: alternative therapeutic strategy for relapsed/refractory CLL.
PMID:日期:2026-09-23Although therapies targeting BTK of BCR-signal are changing the landscape of CLL management, these agents are not curative and resistance can develop. Thus, we searched for other druggable target(s) regulating leukemic B-cell survival for developing alternative therapies. We detected MERTK, a member of the TAM (Tyro3, AXL, MERTK) family receptor tyrosine kinases (RTKs), is aberrantly expressed and constitutively active in CLL cells from ~65% CLL patients (n = 100). Ligation of Gas6, a common ligand for TAM-RTKs, preferentially activated MERTK resulting in activation of NF-κB/AKT/Erk1/2 and BTK in CLL cells. Partial depletion of MERTK in CLL cells reduced P-Erk1/2, P-NF-κB, P-AKT, and P-BTK levels, suggesting that MERTK may crosstalk with BCR-signal. Indeed, MERTK activated BTK by forming a signalosome with CD79a/LYN in CLL cells. Interestingly, stimulation of BCR-signals in CLL cells activated MERTK via CD79a, suggesting that MERTK/BCR-signals are functionally connected. Importantly, targeting MERTK using a high-affinity, pharmacologic inhibitor UNC-2025 induced apoptosis in CLL cells and reduced leukemic burden in vivo. More significantly, ibrutinib-resistant CLL cells expressed high-levels of MERTK and that, UNC-2025 synergistically induced apoptosis when combined with venetoclax. Thus, high MERTK-levels in CLL cells may be associated with ibrutinib-resistance underscoring the potential use of UNC-2025/venetoclax combination in treating relapsed/refractory patients.
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5. C3- and C5-deficient murine cells exhibit severe mitochondrial defects, indicating a pivotal, novel role of innate immunity in regulating hematopoiesis at the electron transfer chain level.
PMID:日期:2026-09-22We recently reported that the functional intracellular complement network, known as the complosome, is expressed in hematopoietic stem/progenitor cells (HSPCs). In our recent work, murine lineage-negative (Lin) bone marrow (BM) mononuclear cells (BMMNC) from C3-KO and C5 mice showed defects in oxygen consumption rate (OCR) and elevated lactate production, along with increased lactate dehydrogenase (LDH) release, indicating dependence on anaerobic glycolysis. Simultaneously, mitochondria from C3 and C5 complosome mutant Lin-BMMNC accumulated fewer MitoTracker probes, suggesting mitochondrial defects. To better understand these changes, we focused on the expression of (i) key enzymes involved in aerobic and anaerobic glycolysis, (ii) genes involved in mitochondrial quality control (MCQ), (iii) the electron transfer chain (ETC) activity of all five ETC complexes, and (iv) TEM analysis of mitochondrial morphology in purified murine Lin BMMNC. Our data confirm that the complosome is important for maintaining proper mitochondrial development and function, as C3 and C5 mutants exhibit severe defects in complex I and III activity and display an increase in the number of immature and damaged mitochondria. To our knowledge, this is the first study conducted on cells enriched in HSPCs to directly demonstrate functional defects in the ETC in C3- and C5 complosome-deficient cells. These data are crucial for all studies that use C3- and C5-deficient mice to investigate immune responses, tissue and organ regeneration, aging, or behavioral processes, and provide solid evidence for a pivotal novel role for innate immunity in regulating hematopoiesis.
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7. Clinical evaluation of AI-assisted quantitative marrow fibrosis assessment using Continuous Indexing of Fibrosis (CIF).
PMID:日期:2026-09-16Assessment of fibrosis is central to the evaluation of diagnostic bone marrow trephine (BMT) biopsies. However, manual fibrosis grading is subjective and only semi-quantitative. We evaluated the clinical utility of a previously developed AI-based quantitative fibrosis assessment tool, Continuous Indexing of Fibrosis (CIF), using ~1000 consecutive BMT biopsies without pre-selection. An international panel of 14 haematopathologists performed manual reads using whole-slide images (WSI) of reticulin-stained slides and two types of CIF-assisted reads (Sequential-assisted and Concurrent-assisted) across three study rounds. The AI-derived CIF scores correlated strongly with the manual consensus MF grade (Spearman ρ = 0.770) and demonstrated good discriminative performance across adjacent MF grade boundaries. The CIF-assisted protocols significantly improved intra-observer and inter-observer agreement compared to manual assessment, without increasing read times. Sequential-assisted reads yielded the largest gain in inter-observer agreement (12.6 percentage points; 95% CI 10.5-14.8) and improved agreement with the consensus reference (3.0 percentage points; 95% CI 0.4-5.7). Both assisted protocols reduced discordance across the clinically significant MF-1 / MF-2 boundary. These findings demonstrate that AI-assisted quantitative bone marrow fibrosis assessment using CIF is reproducible, efficient and well suited for future clinical deployment testing. This supports a future role in standardising routine diagnostic haematopathology and enhancing the sensitivity of fibrosis-based clinical trial endpoints.
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8. SRSF2 P95H induces monocytic priming of human hematopoietic stem and progenitor cells.
PMID:日期:2026-09-14该文献暂无摘要。
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9. Targeting CD38 with bispecific antibody XmAb 18968 in patients with relapsed/refractory acute myeloid leukemia and T-cell acute lymphoblastic leukemia.
PMID:日期:2026-09-14CD38 is a transmembrane glycoprotein highly expressed in acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). XmAb18968 is a novel CD38-CD3 bi-specific T-cell engager with Fc domain modified to reduce non-selective activation of effector cells. In this phase 1 multicenter clinical trial, we evaluated the outcomes of XmAb18968 in adults with relapsed/refractory (RR) AML and T-ALL. Twenty-two patients with AML (n = 13) and T-ALL (n = 9) with a median age of 63 years (range 31-77) were enrolled. Prior lines of therapy (median 3, range 1-8) included venetoclax (77.3%), allogeneic HCT (22.7%), CD7 CAR-T cell therapy and daratumumab (11.1%). Grade ≥3 adverse events included anemia (14%), neutropenia (18%), and thrombocytopenia (14%). No grade ≥3 cytokine release syndrome or neurotoxicity was seen. Overall, 17 patients (AML = 11, ALL = 6) completed at least one cycle of therapy. Among 11 patients with RR-AML, one achieved partial remission (PR) and two achieved MRD negative complete remission (CR). In 6 patients with RR-T-ALL, 4 achieved meaningful improvement in disease burden with 1 clearance of MRD. Median OS was 8.5 months in AML and 8.7 months in T-ALL. XmAb18968 is safe and tolerable with encouraging preliminary efficacy, supporting further investigation of CD38 targeting therapies in this setting (NCT05038644).
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10. Circulating tumor cells identify a disseminated genomic high-risk phenotype within IMS-IMWG 2025 staging in newly diagnosed multiple myeloma.
PMID:日期:2026-09-07The 2025 IMS-IMWG consensus genomic staging (CGS) system has improved genomic risk stratification in newly diagnosed multiple myeloma (NDMM), yet does not capture whether high-risk clones have acquired a disseminated phenotype. We investigated whether circulating tumor cells (CTC) refine CGS and enable longitudinal residual disease monitoring. We retrospectively analyzed 631 MM patients from the NICHE cohort (NCT04645199) who underwent CTC assessment across disease phases. Among 410 patients assessed at diagnosis, CTC were detectable in 63.9% and correlated with both bone marrow plasma cell infiltration and accumulation of high-risk cytogenetic abnormalities. In 359 NDMM patients with adequate follow-up, a cohort-derived CTC threshold of 0.38% independently predicted inferior progression-free survival (PFS) after multivariable adjustment. Importantly, CTC refined prognostic stratification specifically within the CGS high-risk subgroup. Patients with CGS high-risk/CTC-high disease had the shortest PFS, thereby defining a disseminated genomic high-risk phenotype comprising 12.4% (39/314) of evaluable NDMM patients. In follow-up cohorts, detectable CTC were associated with inferior outcomes in 127 patients assessed during non-progressive disease states, whereas combined CTC and bone marrow minimal residual disease assessment stratified outcomes in 120 patients with paired measurements. Overall, CTC-integrated CGS supports minimally invasive baseline risk stratification and longitudinal disease monitoring.