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Titel:

Developmental trajectories and cooperating genomic events define molecular subtypes of BCR::ABL1-positive ALL.

Dokumenttyp:
Journal Article
Autor(en):
Bastian, Lorenz; Beder, Thomas; Barz, Malwine Jeanette; Bendig, Sonja; Bartsch, Lorenz; Walter, Wencke; Wolgast, Nadine; Brändl, Björn; Rohrandt, Christian; Hansen, Björn-Thore; Hartmann, Alina M; Iben, Katharina; Das Gupta, Dennis; Denker, Miriam; Zimmermann, Johannes; Wittig, Michael; Chitadze, Guranda; Neumann, Martin; Schneller, Folker; Fiedler, Walter; Steffen, Björn; Stelljes, Matthias; Faul, Christoph; Schwartz, Stefan; Müller, Franz-Josef; Cario, Gunnar; Harder, Lana; Haferlach, Claudia;...     »
Abstract:
Distinct diagnostic entities within BCR::ABL1-positive acute lymphoblastic leukemia (ALL) are currently defined by the International Consensus Classification of myeloid neoplasms and acute leukemias (ICC): "lymphoid only", with BCR::ABL1 observed exclusively in lymphatic precursors, vs "multilineage", where BCR::ABL1 is also present in other hematopoietic lineages. Here, we analyzed transcriptomes of 327 BCR::ABL1-positive patients with ALL (age, 2-84 years; median, 46 years) and identified 2 main gene expression clusters reproducible across 4 independent patient cohorts. Fluorescence in situ hybridization analysis of fluorescence-activated cell-sorted hematopoietic compartments showed distinct BCR::ABL1 involvement in myeloid cells for these clusters (n = 18/18 vs n = 3/16 patients; P < .001), indicating that a multilineage or lymphoid BCR::ABL1 subtype can be inferred from gene expression. Further subclusters grouped samples according to cooperating genomic events (multilineage: HBS1L deletion or monosomy 7; lymphoid: IKZF1-/- or CDKN2A/PAX5 deletions/hyperdiploidy). A novel HSB1L transcript was highly specific for BCR::ABL1 multilineage cases independent of HBS1L genomic aberrations. Treatment on current German Multicenter Study Group for Adult ALL (GMALL) protocols resulted in comparable disease-free survival (DFS) for multilineage vs lymphoid cluster patients (3-year DFS: 70% vs 61%; P = .530; n = 91). However, the IKZF1-/- enriched lymphoid subcluster was associated with inferior DFS, whereas hyperdiploid cases showed a superior outcome. Thus, gene expression clusters define underlying developmental trajectories and distinct patterns of cooperating events in BCR::ABL1-positive ALL with prognostic relevance.
Zeitschriftentitel:
Blood
Jahr:
2024
Band / Volume:
143
Heft / Issue:
14
Seitenangaben Beitrag:
1391-1398
Volltext / DOI:
doi:10.1182/blood.2023021752
PubMed:
http://view.ncbi.nlm.nih.gov/pubmed/38153913
Print-ISSN:
0006-4971
TUM Einrichtung:
Klinik und Poliklinik für Innere Medizin III, Hämatologie und Onkologie (Prof. Bassermann)
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