Decoding the Complexities of Mixed Phenotype Acute Leukemia with t(v;11q23.3); KMT2A Rearranged

; KMT2A Rearranged”)

Expert Reviewed By: ⁠Dr. Brandon Colby MD

Mixed Phenotype Acute Leukemia (MPAL) is a rare and complex hematologic cancer, characterized by the presence of both lymphoid and myeloid features within the same tumor. One specific subtype of MPAL involves a genetic rearrangement known as t(v;11q23.3); KMT2A rearranged. This article aims to provide an overview of this specific MPAL subtype, focusing on understanding the disease, its diagnosis, and the role of genetic testing in its management.

Understanding Mixed Phenotype Acute Leukemia with t(v;11q23.3); KMT2A Rearranged

MPAL with t(v;11q23.3); KMT2A rearranged is a subtype of acute leukemia that exhibits both lymphoid and myeloid characteristics within the same tumor. This genetic rearrangement involves the KMT2A gene, which plays a crucial role in regulating gene expression and maintaining the normal development of blood cells. The KMT2A gene is located on the long arm of chromosome 11 (11q23.3), and its rearrangement results in the fusion of KMT2A with another gene, leading to the formation of a fusion protein that drives the development of leukemia.

Two recent studies have shed light on the molecular consequences of different KMT2A rearrangements in acute leukemia and their role in lineage determination. The first study, “Biology of t(6;11) Fusion Proteins and Their Role in MLL-Rearranged Acute Leukemia Lineage Determination”, investigates the role of MLL-AF6 fusions in acute leukemia lineage determination. The second study, “FLT3 chimeric antigen receptor T cell therapy induces B to T cell lineage switch in infant acute lymphoblastic leukemia”, explores the potential of FLT3 CAR as a treatment for B-ALL and the unexpected finding that FLT3 CAR T cells induce lineage switch of an infant ALL from a B to T cell phenotype.

Diagnosing Mixed Phenotype Acute Leukemia with t(v;11q23.3); KMT2A Rearranged

Diagnosing MPAL with t(v;11q23.3); KMT2A rearranged can be challenging due to its rarity and the presence of both lymphoid and myeloid features within the same tumor. A combination of morphologic, immunophenotypic, cytogenetic, and molecular diagnostic techniques is typically employed to identify this specific subtype of MPAL. The identification of the KMT2A rearrangement is crucial for the accurate diagnosis of this disease.

Role of Genetic Testing in Diagnosis

Genetic testing is an essential tool in the diagnosis of MPAL with t(v;11q23.3); KMT2A rearranged. It allows for the identification of the specific KMT2A rearrangement and its fusion partner, which is critical for accurate diagnosis and classification of the disease. Genetic testing can be performed using various techniques, such as fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), or next-generation sequencing (NGS).

Using Genetic Testing for Management of Mixed Phenotype Acute Leukemia with t(v;11q23.3); KMT2A Rearranged

Genetic testing not only plays a crucial role in the diagnosis of MPAL with t(v;11q23.3); KMT2A rearranged but also has significant implications for its management. The identification of the specific KMT2A rearrangement and its fusion partner can guide treatment decisions, as certain fusion proteins may be associated with specific clinical features or treatment responses.

Role of Genetic Testing in Treatment Selection

Genetic testing can help identify potential therapeutic targets and guide treatment selection for patients with MPAL with t(v;11q23.3); KMT2A rearranged. For example, the identification of the FLT3 gene as a fusion partner in infant ALL has led to the exploration of FLT3 CAR T cell therapy as a potential treatment option. Additionally, genetic testing can help identify patients who may be eligible for clinical trials investigating novel targeted therapies or immunotherapies.

Role of Genetic Testing in Monitoring Treatment Response and Disease Progression

Genetic testing can also be used to monitor treatment response and disease progression in patients with MPAL with t(v;11q23.3); KMT2A rearranged. By tracking the levels of the fusion transcript or the presence of minimal residual disease (MRD), clinicians can assess the effectiveness of treatment and make adjustments as needed. Furthermore, genetic testing can help identify the emergence of new genetic abnormalities or clonal evolution, which may have implications for disease progression and treatment resistance.

In conclusion, understanding, diagnosing, and using genetic testing for Mixed Phenotype Acute Leukemia with t(v;11q23.3); KMT2A Rearranged is essential for accurate diagnosis, treatment selection, and monitoring of this complex and rare hematologic malignancy.

About The Expert Reviewer

Dr. Brandon Colby MD is a US physician specializing in the personalized prevention of disease through the use of genomic technologies. He’s an expert in genetic testing, genetic analysis, and precision medicine. Dr. Colby is also the Founder of  and the author of ⁠⁠Outsmart Your Genes.

Dr. Colby holds an MD from the Mount Sinai School of Medicine, an MBA from Stanford University’s Graduate School of Business, and a degree in Genetics with Honors from the University of Michigan. He is an Affiliate Specialist of the American College of Medical Genetics and Genomics (⁠⁠ACMG), an Associate of the American College of Preventive Medicine (⁠⁠ACPM), and a member of the National Society of Genetic Counselors (⁠NSGC)