Iain Clark, Ph.D.

Research

Mixed phenotype acute leukemia (MPAL) is one of the most lethal and poorly understood forms of acute leukemia. Defined by co-expression of lymphoid and myeloid markers, MPAL lacks clear genetic subtypes and no reliable framework for risk stratification exists. A key unanswered question in MPAL biology is how genetic mutations—many of which are shared with more treatable leukemias—lead to lineage ambiguity and treatment resistance. Recent work has suggested that MPAL cells converge on a stem-like transcriptional program that correlates with patient survival. However, existing technologies cannot track how mutational evolution drives leukemic cells into this stem-like, therapy-refractory state. To overcome this, we are developing a single-cell platform that simultaneously profiles genomic and transcriptomic information from individual cells. We will apply this technology to MPAL patient samples collected during treatment, remission, and relapse with the goal of reconstructing how sequential mutations shape transcriptional programs, drive clonal evolution, and influence clinical outcomes.