Multiple Lineage Switches in a Pediatric Case With a KMT2A::AFF1-Positive Acute Lymphoblastic Leukemia: How Cell...

Area of Science:

• Hematology
• Oncology
• Molecular Biology

Background:

• Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are distinct hematologic malignancies.
• KMT2A::AFF1 fusion gene is a known driver in infant ALL.
• Lineage plasticity in leukemia is a complex phenomenon.

Observation:

• A 10-year-old female with KMT2A::AFF1-positive ALL presented with recurrent lineage switching to AML and ALL.
• The leukemic clone demonstrated resistance to standard chemotherapy, immunotherapy, and hematopoietic stem cell transplantation.
• Immunoglobulin/T-cell receptor rearrangements persisted throughout the disease course, indicating a common clonal origin.

Findings:

• The case highlights multiple, rare lineage switches in a pediatric ALL patient, defying typical infant-onset patterns.
• Persistent leukemic clone plasticity suggests a unique cell-of-origin capable of bidirectional differentiation.
• High therapy-escaping grade indicates significant resistance mechanisms driven by lineage plasticity.

Implications:

• Understanding the cell-of-origin for such lineage plasticity is crucial for developing targeted therapies.
• This case underscores the need to investigate genetic factors contributing to leukemia cell plasticity.
• Further research into selective pressures driving lineage switching is essential for improving treatment strategies in relapsed leukemia.