What question did this study set out to answer?

January 25, 2026Open Access

Clonal Evolution and Lineage Switch from T‐Cell Acute Lymphoblastic Leukemia to Acute Myeloid Leukemia in Therapy‐Resistant PICALM::MLLT10 Leukemia

Puntos clave

This research aims to understand the clonal evolution and lineage switch from T-cell acute lymphoblastic leukemia (T-ALL) to acute myeloid leukemia (AML) in therapy-resistant cases.
Detailed cytogenetic analysis to identify chromosomal abnormalities.
Mutational profiling to detect genetic mutations and loss of heterozygosity.
Long-term patient follow-up to observe disease progression and lineage switching.
The patient initially achieved complete remission from T-ALL but relapsed as AML six years later.
Cytogenetic findings included del(5q), del(17p), and 17q gain.
Mutational profiling revealed mutations in NF1, EZH2, SMC1A, and PHF6, with some mutations emerging after therapy.

Resumen

ABSTRACT Background PICALM::MLLT10 ‐positive T‐ALL is rare and associated with poor prognosis. Lineage switch to AML is exceptionally uncommon, particularly after long‐term remission. Case Presentation We report an adolescent PICALM::MLLT10 ‐positive T‐ALL with a cortical thymocyte, non‐ETP phenotype. The patient achieved complete remission but relapsed as AML 6 years later. Cytogenetics revealed del(5q), del(17p), and 17q gain. Mutational profiling demonstrated mutations with LOH in NF1 and EZH2 , a hemizygous SMC1A mutation, and a hemizygous PHF6 mutation detected only after subsequent therapy. Conclusion This case illustrates that therapy‐resistant PICALM::MLLT10 progenitors can persist during remission and re‐emerge as AML through lineage switch. The sequential acquisition of cooperating genetic lesions supports clonal evolution and highlights the need for molecular monitoring and novel therapeutic strategies. Trial Registration The authors have confirmed clinical trial registration is not needed for this submission.

Leer artículo completoexternamente

Me gusta

Guardar

Ver artículo completo