nelarabine / Generic mfg. - LARVOL DELTA

Utilization patterns of venetoclax-based regimens for AML in a community based setting & representative populational analyses (ASH 2025) - "In first line setting, 22 patients (52.3%) received Venetoclax with azacitidine, 17 patients 40.1% received decitabine, 2 patients (4.8%) with cladribine and cytarabine, and 2 patients (4.8%) received Venetoclax alone...6 patients (40%) received azacitidine with venetcloax, 6 patients (40%) received decitabine, 1 patient (6.7%) received cytarabine, 1 patient (6.7%) received enasidenib, and one patient (6.7%) received nelarabine, cyclophosphamide, and cytarabine... The median age at diagnosis was 64 years (range 21-86). 47% patients were female gender. 24.5% of patients were Black or African-American, 71.4% were White, 1% were Asian, and 3.1% were more than one race."

Clinical • Acute Myelogenous Leukemia • Febrile Neutropenia • Hepatology • Liver Failure • Neutropenia • Renal Disease • CEBPA • DDX41 • NPM1 • TP53

Predictors of outcome in adult patients with Relapsed/Refractory T-cell acute lymphoblastic leukemia (ASH 2025) - "Common mutations included NOTCH1 (50%), TET2(45.7%), ASXL1 (34.3%), and RAS pathway mutations (24.4%); Complex cytogenetics and KMT2Arearrangements were seen in in 10% and 4%, respectively.Frontline (F/L) regimens included HCVAD (46%), nelarabine-based (34%), pediatric-inspired regimens (9%),and venetoclax (VEN)-based regimens (6%). R/R T-ALL carried poor prognosis, with a median OS of 8.1 months and 2-year OS of only14%. Achieving CR in S1, undergoing SCT, and use of nelarabine were independently associated withimproved survival. In the ETP-ALL subset, nelarabine use and achieving CR remained significant inmultivariate analysis."

Biomarker • Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ASXL1 • KMT2A • NOTCH1 • TET2

Longitudinal clonotype tracking by next-generation sequencing (NGS) based T-cell receptor (TCR) rearrangement measurable residual disease (MRD) assay in frontline adult T-acute lymphoblastic leukemia (ALL) (ASH 2025) - "Most common treatment was combination of hyper-CVAD with nelarabine,pegasparaginase and/or venetoclax (n=33, 87%). After adjusting for non-leukemic tracking sequences, pts with the persistent NGS MRD during theintensive phase of therapy had significantly higher risk of relapse than those who achieved NGS MRDnegativity. Our findings suggest that NGS MRD is prognostic in T-ALL, although more pts with longerfollow-up are needed to determine the prognostic impact of NGS MRD dynamics and outcomes in T-ALL."

Clinical • IO biomarker • Next-generation sequencing • Residual disease • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • TRB • TRG

Molecular subtypes and BH3 mimetic synergy with anti-leukemia agents in T-cell acute lymphoblastic leukemia (ASH 2025) - "In this study, we evaluated the ex vivo cytotoxicity of threeinvestigational BH3 mimetics, namely AZD4320 (BCL2/BCL-XL dual inhibitor), AZ'3202 (BCL-XL inhibitor),and AZD5991 (MCL1 inhibitor), using an imaging-based cell viability assay in a panel of 58 patient-derivedxenograft (PDX) models of T-ALL...These findings highlightthe interplay between molecular subtype and apoptotic signaling and their effects on BH3 mimeticsensitivity in T-ALL.Next, to investigate the therapeutic potential of BH3 mimetics in combination settings for T-ALL, weevaluated the interactions between AZD4320 and key anti-leukemic agents, i.e., asparaginase,prednisolone, nelarabine, and an LCK inhibitor, dasatinib, across 40 T-ALL PDX samples ex vivo...In three T-ALL PDX models, the combination of AZD0466 (a drug-dendrimer conjugateof AZD4320) with asparaginase consistently exhibited greater efficacy compared to monotherapy (vsAZD0466, P = 0.0007, P = 0.015, and P = 0.0006; vs asparaginase, P =..."

Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • BCL2 • BCL2L1

Cell-free application of Deltex1 to suppress hyperactive notch signaling in t-cell acute lymphoblastic leukemia (ASH 2025) - "Transcriptomic analysis revealed a significant decrease in Notch pathway activity andin cell cycle progression of T-ALL that receive nanoparticle treatment. Furthermore, the nanoparticletreatment synergized with existing standard-of-care chemotherapy such as Nelarabine, indicating a novelclinically relevant approach for treating refractory T-ALL."

Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • Targeted Protein Degradation • T-cell Acute Lymphoblastic Lymphoma • NOTCH1

Nelarabine treatment before allogeneic stem cell transplantation was associated with an increased risk of neurological adverse events in patients with T-ALL/lbl: A retrospective study of the kanto study group for cell therapy. (ASH 2025) - "In multivariate analysis, NEL treatment was identified asan independent risk factor for NRM (HR = 5.7; p 50 years) (HR= 3.2; p = 0.023), but not for OS (HR = 2.9; p = 0.055).[Conclusion] These findings suggest that NEL treatment before SCT might be associated with a higher riskof clinically relevant NAEs in T-ALL/LBL patients. Further investigation is warranted to elucidate the riskfactors for NAEs following SCT in patients treated with NEL, and to better define the impact of NEL ontransplant outcomes in a larger cohort."

Adverse events • Retrospective data • Acute Lymphocytic Leukemia • CNS Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoblastic Lymphoma • Lymphoma • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • Vascular Neurology

Outcome of children and adolescents with newly diagnosed T-cell acute lymphoblastic leukemia: Results of DFCI ALL consortium protocol 16-001 (ASH 2025) - "Pts with T-ALLwere classified as initial high-risk (HR) and received multiagent induction chemotherapy, includingdoxorubicin and dexamethasone...Pts assigned to Final VHR received2 intensified Consolidation cycles, including nelarabine, high-dose cytarabine, and etoposide...Pts with ETP/near-ETP experienced high rates of IF, but OS remainedcomparable to non-ETP T-ALL pts. Novel treatment strategies are needed for VHR T-ALL pts, includingthose with high TP2 MRD and/or KMT2A-rearrangements."

Clinical • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • IKZF1 • KMT2A

Venetoclax in combination with hypomethylating agents are effective salvage therapy in relapse/refractory ETP-ALL and near-ETP-ALL (ASH 2025) - "Introduction Limited progress has been made in the treatment of T-lymphoblastic leukaemia/lymphoma (T-ALL/LBL)with a paucity of new agents since the approval of nelarabine 20 years ago...Venetoclax was used at 100 mg daily with an azole antifungal prophylaxis (leading to an effective doses ofabout 400 mg daily) in 13 patients, and 1 patient used venetoclax 200mg daily without concurrent azole.HMA used included azacitadine (75mg/m2 for 7 days/cycle, N=9), decitabine (20mg/m2 for 5 days/cycle,N=4), and sequential decitabine and azacitadine (N=1)...Haematological toxicities are common but manageable. Patients with prior exposure tovenetoclax might have an inferior response to VEN-HMA."

Combination therapy • IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Septic Shock • T Acute Lymphoblastic Leukemia • BCL2L1

Optimization of upfront therapy for adult acute lymphoblastic leukemia: a paradigm shift toward immunotherapy. (PubMed, Med Oncol) - "Targeted immune therapies like blinatumomab, inotuzumab ozogamicin (InO), rituximab, and nelarabine are being combined with traditional chemotherapy protocols to enhance remission rates and minimal residual disease (MRD) negativity while decreasing toxicities...Ph + ALL patients receive standard treatment with multi-agent chemotherapy and TKIs dasatinib or ponatinib and blinatumomab as part of their frontline therapy to enhance molecular responses and minimize the requirement for allogeneic hematopoietic stem cell transplantation (allo-HCT)...The practice of testing MRD and genomic profiling at diagnosis revolutionized treatment approaches by allowing personalized curative strategies for all patients. Research on clinical trials aims to establish the best sequence of targeted therapies and CAR T-cell therapy for high-risk and MRD-positive patients to achieve longer survival rates with reduced toxicity and less dependence on allo-HCT in first remission."

Journal • Review • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • Transplantation • CD20

A Phase I/II Study of Mini-Hyper-CVD, Venetoclax and Navitoclax in Patients with Relapsed/Refractory Philadelphia Chromosome-Negative Acute Lymphoblastic Leukemia (ASH 2024) - "Pts with CD20+ ALL also received up to 8 doses of rituximab...Among the 12 pts with B-cell ALL, all had received prior blinatumomab and 9 (75%) had received prior inotuzumab ozogamicin; among the 10 pts with T-cell ALL/LBL, 5 (50%) had received prior nelarabine...Notably, all 3 pts with R/R ETP ALL achieved CR. While response rate and survival appear better than historical expectations with chemotherapy alone in this population, these outcomes appear similar to those achieved with mini-hyper-CVD + venetoclax in a similar cohort of pts with R/R Ph- ALL (Short NJ et al Blood Adv 2023), questioning the benefit of adding a Bcl-xL inhibitor to this regimen."

Clinical • P1/2 data • Acute Lymphocytic Leukemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Neutropenia • Oncology • BCL2 • BCL2L1 • CD20

Augmented Hyper-CVAD (AHCVAD), a Pediatric Inspired Regimen for Adults Younger Than 50 Years of Age with Acute Lymphoblastic Leukemia (ALL), Yields High Rates of MRD Negativity, Favorable 3-Year Overall Survival Regardless of Allogeneic Stem Cell Transplant (ASCT): A Single Center Experience (ASH 2024) - "Similar to pediatric regimens, AHCVAD uses intensified doses of vincristine, dexamethasone, and pegaspargase and shows activity in relapsed pts with ALL (Faderl S et al : Clin Lymphoma Myel Leuk 2011)...Pts with CD20+ ALL also received Rituximab at 375 mg/m2 on days 1 and15 of cycles 1 to 4. In pts with T-ALL, two cycles of Nelarabine were given following AHCVAD cycles 4 and 5, respectively, and repeated during maintenance cycles 12 and 24...Those who didn't achieve MRD negativity after 2 cycles were switched to blinatumomab or inotuzumab ozogamicin...The augmentation of the hyper-CVAD backbone in this fashion may be more feasible in the community setting than other pediatric protocols. However, intensive monitoring with appropriate antibiotic, antiviral prophylaxis and growth factor support is required given significant toxicities observed."

Clinical • Minimal residual disease • Acute Lymphocytic Leukemia • Burkitt Lymphoma • Cardiovascular • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • Thrombosis • Transplantation • ABL1 • BCR • CD20

E2F transcription factors as multimodal biomarkers for pan-cancer management. (PubMed, Sci Rep) - "There existed a positive correlation between E2F2 expression level and Dasatinib sensitivity, negatively related to drug sensitivity of Nelarabine, XK-469, Cyclophosphamide, etc. Pazopanib, Doxorubicin, and Paclitaxel sensitivity was all positively associated with E2F5 expression. According to these analysis and validation results, E2F genes are relevant to the occurrence and progression of various cancers, which may be biomarkers for tumor diagnostics and prognosis. The discovery of new therapeutic targets can lead to reshaping TME to promote tumor-suppressive metastasis rather than tumor-friendly metastasis."

Biomarker • IO biomarker • Journal • Pan tumor • Tumor mutational burden • Bladder Cancer • Genito-urinary Cancer • Microsatellite Instability • Oncology • Solid Tumor • E2F2 • E2F5 • E2F7 • MSI • TMB

Oncogenetic-Driven Targeted Therapy for Relapsed/Refractory T-Cell Acute Lymphoblastic Leukemia : A French ALL-Target Observatory Report (ASH 2023) - P | "In relapse/refractory (R/R) patients, standard of care treatments, including nelarabine, yield response rate of about 20-40% and responses are of short duration...For example, TTOs included Tofacitinib and Venetoclax (Tofa/Ven) in case of IL7R (CD127) expression or IL7R-pathway alterations (IL7RALT), 5-azacytidine and Venetoclax (Aza/Ven) in case of T-ALL/LL with epigenetic regulators alterations (DNMT3A, ASXL1, PHF6, TET2, PRC2, IDH1/2, SRSF2...) or Temsirolimus, Erwinase and Venetoclax (Tem/Erw/Ven) in case of PI3K signaling pathway alterations (PI3KALT)...Twenty-five patients received a TTO, including 14 Aza/Ven (56%), 8 Tofa/Ven (32%), 2 Tem/Erw/Ven (8%) and 1 Trametinib/Ven (4%)...A better knowledge of the oncogenetic landscape of T-ALL, and a close collaboration between clinicians and biologists, resulted in individualized treatment strategies. With a 3 months cumulative incidence of response of 70%, TTOs appear to be a promising approach in R/R T-ALL."

IO biomarker • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • ASXL1 • ATM • BCL2 • DNMT3A • IDH1 • IDH2 • IL7R • PHF6 • SRSF2 • TET2 • TP53

A Bibliometric Analysis of Drug Resistance in Pediatric Acute Lymphoblastic Leukemia. (PubMed, Adv Biomed Res) - "Based on the thematic map, the keywords of the motor themes were clofarabine, nelarabine, daunorubicin, vincristine, and microRNA, illustrating the need for further investigation of their clinical applications and the underlying mechanisms of resistance to these agents. Medical researchers have been attracted to different aspects of drug resistance in pediatric ALL. This bibliometric analysis reflects the current state of research on drug resistance in pediatric ALL and draws attention to critical concerns that require further investigation."

Journal • Acute Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics

Donor Lymphocyte Infusions in Acute Lymphoblastic Leukemia: A Single-Center Retrospective Analysis (ASH 2024) - "All but 2 patients have received an in vivo T cell depletion either with ATG, or post-transplant cyclophosphamide (for MMUD and HAPLO)...They received a median of 4 DLIs (1-12); DLIs were given in association with TKI in Ph+ ALL patients, with blinatumomab in 1 Ph- ALL case, with nelarabine in 1 T-ALL patient and with off-label bortezomib in 1 T-ALL patient...They received a median of 3 DLIs (2-4), given with TKI in Ph+ B-ALL, inotuzumab in Ph- ALL and radiotherapy in T-ALL...DLI can be an active and safe treatment for ALL, especially if used in the prophylactic/pre-emptive setting and in combination with other therapies. Better evaluation of DLI efficacy in prospective clinical trials is needed in the era of MRD monitoring and novel agents."

Retrospective data • Acute Graft versus Host Disease • Acute Lymphocytic Leukemia • Chronic Graft versus Host Disease • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • T Acute Lymphoblastic Leukemia

Survival and Therapeutic Outcomes in T-Cell Prolymphocytic Leukemia (T-PLL): A Collaborative Multi-Center Study Cohort (ASH 2024) - "Other active second-line treatments included : pentostatin (n=23; 44% ORR, 17% CR), ruxolitinib-based regimens (n=4; 25% ORR, 0% CR), venetoclax-based regimens (n=13; 39% ORR, 8% CR), bendamustine (n=10; 30% ORR, 0% CR), and nelarabine (n=4; 75% ORR, 50% CR)...Conclusions : In this large, multi-center study of T-PLL, frontline treatment with a combination of alemtuzumab/pentostatin improved response rates and OS...Intriguingly, TCL1A+, and CD4- T- PLL had worse OS/PFS, and scRNAseq confirmed unique molecular signatures in these populations, suggesting these represent novel molecular subtypes of T-PLL with prognostic significance. These studies form the foundation for future, targeted, therapeutic studies in this rare, aggressive disease with few treatment options."

Clinical • Hematological Malignancies • Leukemia • Oncology • Prolymphocytic Leukemia • CD4 • CD8 • TCL1A

Integrating Genomics and Functional Phenotypes to Refine Risk Assessment in Acute Myeloid Leukemia across the Age Spectrum: Insights from Singapore (ASH 2024) - "For DBP, nine pediatric AML tumors were treated with cytarabine, daunorubicin, etoposide, and fludarabine, while 12 T-ALL samples were treated with nelarabine, vincristine, dasatinib, asparaginase, and dexamethasone...Direct mitochondrial sensitivity to venetoclax in lymphoblasts was higher in T-ALL (n=29) than in B-ALL (n=47). Lymphoblasts showed greater direct mitochondrial sensitivity to navitoclax, suggesting the potential use of dual inhibition of BCL2 and BCL-XL in ALL...The consistent sensitivity of lymphoblasts and myeloblasts to BCL-2 inhibition across age groups and lineages suggests the broad applicability of our approach. By integrating cellular vulnerabilities to anti-apoptotic proteins into clinical assessments, we may significantly improve treatment decision-making and risk stratification in acute leukemia."

IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • BCL2L1 • MCL1

Frontline Venetoclax Therapy for 18-Year-Old Male with Ataxia Telangiectasia and Early T-Cell Precursor Acute Lymphoblastic Leukemia (ASH 2023) - "Induction chemotherapy was given as per COG AALL1231 protocol with dose modifications including 50% decrease in vincristine and cyclophosphamide...He was given 150 mg/m2 for 7 days directly followed by nelarabine...Patients with AT have increased risk of toxicity from chemotherapy agents which requires dose modifications in their chemotherapy regimen. Venetoclax augmentation may be a viable approach for patients with AT or DNA repair disorders."

IO biomarker • Acute Lymphocytic Leukemia • Ataxia • CNS Disorders • Fatigue • Hematological Malignancies • Immunology • Leukemia • Movement Disorders • Oncology • Primary Immunodeficiency • CD38 • CD5 • CD7 • CREBBP • ICAM1 • NCAM1 • NOTCH1 • PTPRC • SRSF2

Combination Therapy with Nelarabine, Peg-Asparaginase and Venetoclax for Adults Patients with Relapsed/Refractory T-Cell ALL (ASH 2024) - "The median OS of the whole cohort was 9.1 months and the median RFS of the responders was 23 months. NEL-PEG-VEN regimen is an effective therapy in getting this difficult to treat population into a remission, allowing them to proceed with a potentially curative allo-SCT."

Clinical • Combination therapy • Oncology • T Acute Lymphoblastic Leukemia • FBXW7 • NOTCH1 • TP53

Nelarabine (NEL), Pegylated Asparginase (PEG) and Venetoclax (VEN) Incorporated to HCVAD Chemotherapy in the Frontline Treatment of Adult Patients with T-Cell Acute Lymphoblastic Leukemia/Lymphoblastic Lymphoma (T-ALL/T-LBL) (ASH 2023) - "Pts received 8 cycles (C) of HCVAD (C 1,3, 5, 7) alternating with high dose Ara-C and methotrexate (MTX) (C 2, 4, 6, 8) at approximately 3-week intervals...After the completion of the intensive phase; pts in all cohorts received 30 cycles of maintenance therapy with monthly POMP (prednisone, vincristine, MTX, prednisone) and early intensification with NEL/PEG on C6 and 7 and late intensification with MTX/PEG in C18 and HCVAD on C19... The ongoing phase 2 trial of NEL, ASP, VEN added to the HCVAD regimen shows promising long-term survival in adult pts with T-ALL/LBL with 3-yr OS of 76%-88% in pts treated with HCVAD+NEL+PEG +/- VEN. Larger prospective trials and longer follow-up are needed to demonstrate further benefit."

Clinical • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma

The AKR1C3-Activated Prodrug, Achm-025, Eradicates Disease in Preclinical Models of Aggressive T-Cell Acute Lymphoblastic Leukemia (ASH 2023) - "ACHM-025 was designed to improve drug specificity and minimize toxicity observed with currently used DNA alkylating agents, such as cyclophosphamide (CPM), a prodrug which is activated systemically via liver enzymes...For the consolidation therapy comparison, ACHM-025 (IP Days 0, 7) or CPM (IP Days 0, 7) combined with cytarabine (Ara-C; IP Days 0-4, 7-11) and 6-mercaptopurine (6MP; IP Days 0-4, 7-11) were assessed against a T-ALL PDX derived from a patient at relapse... ACHM-025 exerted profound in vivo efficacy against T-ALL PDXs and eradicated the disease in 7 aggressive T-ALL PDXs. ACHM-025 was significantly more effective than CPM both as a single agent and when used in combination with Ara-C/6MP. Notably, ACHM-025 in combination with nelarabine was curative when used to treat a chemoresistant T-ALL PDX in vivo."

Preclinical • Acute Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • AKR1C3 • PTPRC

Frontline Consolidation with Nelarabine for Adults with High-Risk T-Cell Acute Lymphoblastic Leukemia. Results of the Graall-2014/T Atriall Phase 2 Study (ASH 2023) - "NELA was given at 1,500 mg/sqm/day at day 1,3 and 5 in combination with etoposide and cyclophosphamide for a maximum of 5 courses during consolidation (2 cycles) and maintenance (3 cycles). While NELA did not yield an overall improved outcome in the study population, benefits were observed in favorable MRD responders and non-ETP patients. Additional prospective studies are needed to further delineate the specific patient subgroups that might benefit from NELA."

Clinical • P2 data • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Hematological Malignancies • Leukemia • Oncology • T Acute Lymphoblastic Leukemia • T-cell Acute Lymphoblastic Lymphoma • Transplantation • FBXW7 • NOTCH1 • PTEN

Outcome of an Urban Cohort of North American Adult T-Cell Leukemia/Lymphoma Patients (ASH 2024) - "Ten (45%) patients received CNS prophylaxis including intrathecal (IT)-MTX 50%, HD-MTX 30%, and IT-cytarabine 20%...Patients attaining CR or PR who were eligible for alloSCT based on donor availability and comorbidity score, received bridging therapy with several cycles of brentuximab (if CD30+) or nelarabine...Within the limitations of a single institution cohort, we report that age and WBC count at diagnosis are associated with a worse OS. Accurate diagnosis and early referral to centers with transplant and clinical trial availability is key to management of ATLL patients."

Clinical • Adult T-Cell Leukemia-Lymphoma • Candidiasis • Hematological Malignancies • Hepatology • Human Immunodeficiency Virus • Infectious Disease • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Pulmonary Disease • Respiratory Diseases • TNFRSF8 • TP53

The Impact of Age and Genomics on Drug Sensitivity in 1,076 Children and Adults with B-Cell Acute Lymphoblastic Leukemia (ASH 2023) - "Among 21 drugs, seven showed significant differences in overall LC50 between children and adults (P<0.05 after Bonferroni correction): children displayed higher sensitivity to asparaginase, prednisolone, mercaptopurine, daunorubicin, and inotuzumab, while adults showed higher sensitivity to dasatinib and nelarabine...In the KMT2A subtype, cases in C-a exhibited an over-representation of the KMT2A::AFF1 fusion, and resistance to mercaptopurine (P=0.029), prednisolone (P=0.0039), vincristine (P=0.046) and cytarabine (P=0.0037)...In conclusion, these studies have revealed important new insights into the pharmacogenomic basis of age-related differences in B-ALL treatment response. These results indicate that both inter- and intra-subtype heterogeneity contribute to inferior prognosis in adults with ALL, but also point to therapeutic opportunities to improve their outcomes."

Clinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • ABL1 • AFF1 • CRLF2 • DUX4 • KMT2A

Revolutionizing B-ALL Cell Line Development: Novel Generation to Uncover Therapeutic Vulnerabilities (ASH 2024) - "LH lines showed resistance to many cytotoxic drugs, especially birinapant, inotuzumab, dexamethasone, and nelarabine...Additionally, we found LH samples also respond well to vincristine and JQ1, suggesting new vulnerabilities. Surprisingly, BCR : : ABL1+/BCR : : ABL1-like samples with IK6 were sensitive to dexamethasone and gilteritinib compared to those with wild type IKZF1, though complete cell eradication was not achieved even at high dosage, indicating combined therapy would be beneficial.In summary, we developed a new approach, generating 21 B-ALL cell lines spanning 11 subtypes. Combined with commercial lines, we now have seven LH lines, eight BCR : : ABL1-like lines, five HLF-r lines, and four near haploid lines to further study the mechanisms and therapeutic vulnerabilities of these high-risk B-ALL subtypes. These models provide an important resource for identifying dependencies and therapeutic vulnerabilities."

Preclinical • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology • ABL1 • CRLF2 • IKZF1 • KMT2A • MEF2D • NTRK3 • NUTM1 • PAX5 • PBX1 • TCF3 • ZEB2