Lineage Switch from B-ALL to AML in a Patient with KMT2A Rearrangement Presenting as Leukemia Cutis: A Rare Case Report

Summary: Acute leukemia (AL) with a lineage switch (LS) is rare and associated with poor prognosis. Studies suggest that the lineage plasticity of leukemic stem cells is driven by genetic alterations, such as KMT2A rearrangements. A 35-year-old female was diagnosed with B-ALL in July 2017 on bone marrow studies. FISH studies on peripheral blood revealed a KMT2A (MLL, 11q23) rearrangement. She was enrolled in a Phase III Randomized Trial of Blinatumomab for Newly Diagnosed BCR-ABL negative B lineage Acute Lymphoblastic Leukemia in Adults. Bone marrow studies done on day 28 post-initiation of therapy demonstrated complete response. In October 2017, she developed non-pruritic papules and nodules on her extremities and face. A skin biopsy confirmed leukemia cutis with a KMT2A rearrangement, as shown by FISH studies. A subsequent skin biopsy revealed dense dermal and subcutaneous infiltrates of large blastoid cells with atypical morphology, showing positivity for CD33, CD117, CD56, CD68 (partial), CD43, and myeloperoxidase (~5%), while B-lymphoblastic lineage markers, including CD19, PAX5, and TdT, were negative, consistent with AML with monocytic differentiation. This case demonstrates the post-therapeutic lineage plasticity of leukemic stem cells with KMT2A rearrangements, and the need for a deeper understanding of the mechanisms of phenotypic change in the disease.