Here, we describe the immunoglobulin and T cell receptor (Ig/TCR) molecular rearrangements identified as a leukemic clone hallmark for minimal residual disease assessment in relation to mutational status in 171 Ph-negative Acute Lymphoblastic Leukemia (ALL) adult patients at diagnosis. The presence of a alterations, which represents a marker of poor prognosis, was strictly correlated with an immature DH/JH rearrangement of the immunoglobulin receptor ( < 0.0001). Furthermore, -mutated patients were classified as pro-B ALL more frequently than their wild-type counterpart (46% vs. 25%, = 0.05). Although the reasons for the co-presence of immature Ig rearrangements and mutation need to be clarified, this can suggest that the alteration in is acquired at an early stage of B-cell maturation or even at the level of pre-leukemic transformation.
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http://dx.doi.org/10.3390/genes11090960 | DOI Listing |
Blood Adv
January 2025
University of Texas M.D. Anderson Cancer Center, Houston, Texas, United States.
Measurable residual disease (MRD) is a powerful predictor of clinical outcomes in acute lymphoblastic leukemia (ALL). In addition to its clear prognostic importance, MRD information is increasingly used in clinical decision algorithms to guide therapeutic interventions. While it is well-established that achievement of MRD-negative remission is an important endpoint of ALL therapy, the prognostic and therapeutic implications of MRD in an individual patient are influenced by both disease-related factors (e.
View Article and Find Full Text PDFCells
January 2025
School of Biomedical Sciences, The University of Western Australia, Crawley, WA 6009, Australia.
Acute lymphoblastic leukaemia is the most common childhood malignancy that remains a leading cause of death in childhood. It may be characterised by multiple known recurrent genetic aberrations that inform prognosis, the most common being hyperdiploidy and t(12;21) . We aimed to assess the applicability of a new imaging flow cytometry methodology that incorporates cell morphology, immunophenotype, and fluorescence in situ hybridisation (FISH) to identify aneuploidy of chromosomes 4 and 21 and the translocation .
View Article and Find Full Text PDFLeukemia
January 2025
Australian Centre for Blood Diseases (ACBD), School of Translational Medicine, Monash University, Melbourne, VIC, Australia.
Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL) is an immature subtype of T-cell acute lymphoblastic leukemia (T-ALL) commonly show deregulation of the LMO2-LYL1 stem cell transcription factors, activating mutations of cytokine receptor signaling, and poor early response to intensive chemotherapy. Previously, studies of the Lmo2 transgenic mouse model of ETP-ALL identified a population of stem-like T-cell progenitors with long-term self-renewal capacity and intrinsic chemotherapy resistance linked to cellular quiescence. Here, analyses of Lmo2 transgenic mice, patient-derived xenografts, and single-cell RNA-sequencing data from primary ETP-ALL identified a rare subpopulation of leukemic stem cells expressing high levels of the cytokine receptor FLT3.
View Article and Find Full Text PDFJCO Glob Oncol
January 2025
Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Canada.
Purpose: Patients with adolescent and young adult (AYA) cancer are recognized as a vulnerable subpopulation in high-income countries (HICs). Although survival gaps between HIC and low- and middle-income country (LMIC) children with cancer are well described, LMIC AYAs have been neglected. We conducted a systematic review to describe cancer outcomes among LMIC AYAs.
View Article and Find Full Text PDFInt J Hematol
January 2025
Department of Hematology, The 920th Hospital of Joint Logistics Support Force, No.212, Da Guan Road, Xishan District, Kunming, 650100, Yunnan, China.
Background: The treatment of relapsed/refractory T cell acute lymphoblastic leukemia (R/R T-ALL) is a significant challenge in hematologic oncology, and no standard salvage treatment plan exists. Both Chinese and international clinical guidelines recommend combination chemotherapy including venetoclax.
Methods: Efficacy and safety of venetoclax, azacitidine, homoharringtonine, cytarabine, and aclarubicin (VA-HAA) combination therapy were retrospectively analyzed in 3 patients with R/R T-ALL at the Department of Hematology, 920th Hospital of the Joint Logistics Support Force, Chinese People's Liberation Army.
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