Multilineage involvement in KMT2A-rearranged B acute lymphoblastic leukaemia: Cell-of-origin, biology, and clinical implications Journal Article
| Authors: | Aypar, U.; Dilip, D.; Gadde, R.; Londono, D. M.; Liu, Y.; Gao, Q.; Geyer, M. B.; Derkach, A.; Zhang, Y.; Glass, J. L.; Roshal, M.; Xiao, W. |
| Article Title: | Multilineage involvement in KMT2A-rearranged B acute lymphoblastic leukaemia: Cell-of-origin, biology, and clinical implications |
| Abstract: | 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. |
| Keywords: | adolescent; adult; child; clinical article; controlled study; event free survival; human tissue; preschool child; aged; child, preschool; middle aged; young adult; human cell; overall survival; genetics; cancer patient; comparative study; flow cytometry; gene; in situ hybridization, fluorescence; bone marrow; prevalence; cohort analysis; pathology; retrospective study; cell lineage; stem cell; fluorescence in situ hybridization; gene rearrangement; immunoglobulin gene; infant; minimal residual disease; histone-lysine n-methyltransferase; human genome; precursor cell lymphoblastic leukemia-lymphoma; hematopoietic stem cell; bcr abl protein; transcriptome; fusion proteins, bcr-abl; cell selection; histone lysine methyltransferase; principal component analysis; mixed lineage leukemia protein; myeloid-lymphoid leukemia protein; disease burden; humans; human; male; female; article; rna sequencing; differential gene expression; b cell acute lymphoblastic leukemia; gene set enrichment analysis; kmt2a gene; precursor b-cell lymphoblastic leukemia-lymphoma; bcr abl1 gene; kmt2a protein, human |
| Journal Title: | Histopathology |
| Volume: | 85 |
| Issue: | 2 |
| ISSN: | 0309-0167 |
| Publisher: | Wiley Blackwell |
| Date Published: | 2024-08-01 |
| Start Page: | 310 |
| End Page: | 316 |
| Language: | English |
| DOI: | 10.1111/his.15203 |
| PUBMED: | 38686611 |
| PROVIDER: | scopus |
| PMCID: | PMC11246803 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors are MSK author: Umut Aypar and Wenbin Xiao -- Source: Scopus |
