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467
MLL-Rearranged Acute Lymphoblastic Leukemia.
Firas El Chaer1, Michael Keng1, Karen K Ballen2
1Department of Medicine, Division of Hematology and Oncology, University of Virginia School of Medicine, 1215 Lee Street, Charlottesville, VA, 22903, USA.
Current Hematologic Malignancy Reports
|May 1, 2020
Summary
Rearrangements of the KMT2A gene (MLL-r-ALL) are common in acute lymphoblastic leukemia, particularly in infants, and are linked to aggressive disease and poor prognosis. Novel therapeutic targets are being explored to overcome drug resistance in MLL-r-ALL.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- KMT2A (MLL) gene rearrangements are detected in 10% of adult and 5% of pediatric ALL cases.
- Commonly translocated genes include AFF1, MLLT3, and MLLT1.
- MLL-rearranged ALL (MLL-r-ALL) exhibits a bimodal incidence, peaking in infancy and again with increasing age.
Purpose of the Study:
- To review the clinical presentation, risk stratification, and treatment strategies for MLL-r-ALL.
- To discuss drug resistance mechanisms and novel therapeutic targets in MLL-r-ALL.
Main Methods:
- Literature review of MLL-r-ALL focusing on clinical aspects and therapeutic strategies.
- Analysis of drug resistance mechanisms and emerging treatment targets.
Main Results:
- MLL-r-ALL is associated with hyperleukocytosis, aggressive behavior, early relapse, CNS involvement, and poor prognosis.
- Cells show resistance to corticosteroids and L-asparaginase but sensitivity to cytarabine.
- Potential targets include FLT3, MEK, HDAC, BCL-2, MCL-1, proteasome, Dot1L, and CDK inhibitors.
Conclusions:
- MLL-r-ALL presents unique challenges due to its aggressive nature and drug resistance.
- Targeted therapies and novel agents offer promise for improved treatment outcomes in MLL-r-ALL.
