Inv(11)(q21q23); KMT2A-MAML2, a Recurrent Genetic Abnormality in T-Cell Therapy–related Acute Lymphoblastic Leukemia

Abstract

T-cell therapy–related acute lymphoblastic leukemia (T-t-ALL) is a rare condition associated with previous cytotoxic therapy for another disease. Here we report T-t-ALL with inv(11)(q21q23), which involves KMT2A and MAML2, a transcriptional coactivator of NOTCH proteins, that occurred after chemotherapy for Philadelphia chromosome–positive B-cell acute lymphoblastic leukemia. This case describes the youngest patient with T-t-ALL harboring inv(11)(q21q23) and is the first independent report following an initial series also occurring in children. Our results lend further support to the observation that the KMT2A-MAML2 fusion gene resulting from inv(11)(q21q23) is likely a recurrent cytogenetic abnormality in T-t-ALL and appears to be associated with pediatric cases.

Pan-Cancer Landscape Analysis Reveals Recurrent KMT2A-MAML2 Gene Fusion in Aggressive Histologic Subtypes of Thymoma

“…To our knowledge, only 8 patient cases have been reported, including 2 of acute myeloid leukemia, 2 of myelodysplastic syndrome, and 4 of acute lymphoblastic leukemia. [17][18][19][20][21][22] Reported fusion proteins in these patient cases involved regions similar to those identified in our cohort, with the exception of 2 patient cases reported by Metlzer et al 21 with MAML2 breakpoints in introns 2 and 3.…”

KMT2A‐MAML2 rearrangement emerged and regressed during neuroblastoma therapy without leukemia after 12.8‐year follow‐up

“…The eight patients with therapy‐related KMT2A‐MAML2 leukemia/MDS differ from this patient. The primary cancer was leukemia 15,16,21–23 except in two patients 20,24 . None had neuroblastoma.…”

“…Four cases of therapy‐related T‐cell acute lymphoblastic leukemia (ALL), 15,20,21 two cases of therapy‐related AML, 16,22 and one case each of therapy‐related myelodysplastic syndrome (MDS), 23 therapy‐related B‐cell ALL, 24 de novo MDS, 16 and T‐cell ALL that underwent lineage switch to acute myelogenous leukemia (AML) 23 with KMT2A‐MAML2 or inv(11)(q21q23) have been reported. KMT2A‐MAML2 also occurs in aggressive thymoma subtypes 25 .…”

“…Why leukemia did not occur is unknown. The identical transcript occurred in therapy‐related leukemias 16,21 and thymomas 25 . Why this transcript was associated with leukemia in other patients, and why expression was low level are uncertain.…”