Multilineage involvement in KMT2A-rearranged B acute lymphoblastic leukaemia: cell-of-origin, biology, and clinical implications.

Autor: Aypar U; Department of Pathology and Laboratory Medicine, Cytogenetics Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Dilip D; Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Gadde R; Department of Pathology and Laboratory Medicine, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Londono DM; Department of Pathology and Laboratory Medicine, Cytogenetics Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Liu Y; Department of Pathology and Laboratory Medicine, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Gao Q; Department of Pathology and Laboratory Medicine, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Geyer MB; Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Derkach A; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Zhang Y; Department of Pathology and Laboratory Medicine, Cytogenetics Laboratory, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Glass JL; Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Roshal M; Department of Pathology and Laboratory Medicine, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Xiao W; Department of Pathology and Laboratory Medicine, Hematopathology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Jazyk: angličtina
Zdroj: Histopathology [Histopathology] 2024 Aug; Vol. 85 (2), pp. 310-316. Date of Electronic Publication: 2024 Apr 30.
DOI: 10.1111/his.15203
Abstrakt: Aims: B lymphoblastic leukaemia/lymphoma (B-ALL) is thought to originate from Pro/Pre-B cells and the genetic aberrations largely reside in lymphoid-committed cells. A recent study demonstrated that a proportion of paediatric B-ALL patients have BCR::ABL1 fusion in myeloid cells, suggesting a chronic myeloid leukaemia (CML)-like biology in this peculiar subset of B-ALL, although it is not entirely clear if the CD19-negative precursor compartment is a source of the myeloid cells. Moreover, the observation has not yet been extended to other fusion-driven B-ALLs.
Methods and Results: In this study we investigated a cohort of KMT2A-rearranged B-ALL patients with a comparison to BCR::ABL1-rearranged B-ALL by performing cell sorting via flow cytometry followed by FISH (fluorescence in situ hybridization) analysis on each of the sorted populations. In addition, RNA sequencing was performed on one of the sorted populations. These analyses showed that (1) multilineage involvement was present in 53% of BCR::ABL1 and 36% of KMT2A-rearranged B-ALL regardless of age, (2) multilineage involvement created pitfalls for residual disease monitoring, and (3) HSPC transcriptome signatures were upregulated in KMT2A-rearranged B-ALL with multilineage involvement.
Conclusions: In summary, multilineage involvement is common in both BCR::ABL1-rearranged and KMT2A-rearranged B-ALL, which should be taken into consideration when interpreting the disease burden during the clinical course.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: