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MLL Gene Rearrangements in Pediatric AML: Case Report

By: Justine Landin, PhD
Posted: Wednesday, June 16, 2021

Patients with acute myeloid leukemia (AML) commonly express cytogenetic abnormalities, including mixed-lineage leukemia (MLL) gene rearrangements. MLL rearrangements are found in 15% to 20% of pediatric AML cases and may lead to poorer outcomes compared with leukemias not related to this genetic rearrangement. In a case study published in the Journal of Medical Case Reports, a patient with pediatric AML and two different MLL rearrangements received chemotherapy, reduction therapy, and a bone marrow transplant but did not survive.

“Heterogeneity of these cytogenetic abnormalities makes it difficult to determine how to approach patients from a treatment standpoint. This difficulty is further complicated when patients have more than a single MLL rearrangement,” stated coauthors Mary McGrath, MD, of the University of Michigan, Ann Arbor, and Gayle Smink, MD, of Penn State Children’s Hospital, Hershey.

A 10-year-old girl with no family record of childhood illness or cancer presented with a 2-week history of excessive bruising and pallor. A complete blood cell count and peripheral blood flow cytometry revealed consistencies with AML. Chromosomal analyses indicated she had two unique MLL rearrangements: t(9;11)(p22;q23) in 88.4% of cells and t(11;19)(q23;p13.3) in 84.4% of cells. Further, 86% of nuclei had MLL gene fusions of both MLLLT3/MLL (KMT2A) and MLL (KMT2A/MLLT1).

The Children’s Oncology Group AAML1031 Arm A regimen was utilized, as the combination of MLL rearrangements was unknown. Following her first induction cycle, she was classified as low risk, and MLL gene fusions were no longer detected. She subsequently completed three rounds of chemotherapy. Five months later, the patient had an isolated bone marrow relapse. Cytogenetic analysis indicated the return of both types of MLL fusions in 90% of nuclei. Her cancer was refractory to multiple re-induction therapies, and therefore she was enrolled in a phase I clinical trial, receiving a haploidentical bone marrow stem cell transplant. Unfortunately, due to florid relapse a few months after transplant, the patient died of the disease.

Disclosure: The study authors reported no conflicts of interest.


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