Cell Lineage Analysis of Acute Leukemia Relapse Demonstrates Genetic Heterogeneity

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(ChemotherapyAdvisor) – Systematic reconstruction of cell lineage trees of patients with leukemia has identified diverse relapse mechanisms that indicate more than one lineage can promote relapse in the same patient, according to a study published in Blood online May 29.

Prof. Ehud Shapiro, of Weizmann Institute of Science, Rehovot, Israel, and colleagues used a high-throughput method utilizing neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees. They then applied this method “to hundreds of cells of human acute leukemia harvested from multiple patients at diagnosis and at relapse,” they wrote.

At relapse, patients with acute myeloid leukemia had leukemia cells that were shallow (i.e., they rarely divided) compared to cells at diagnosis “and were closely related to their stem cell subpopulation, implying that in these instances relapse might have originated from rarely dividing stem cells,” Dr. Shapiro reported.

In contrast, no differences in cell depth were observed between diagnosis and relapse in patients with acute lymphoid leukemia. In one case of chronic myeloid leukemia, at blast crisis, the majority of the cells at relapse were mismatch-repair deficient.

“We know that in many cases, chemotherapy alone is not able to cure leukemia,” Dr. Shapiro said. “Our results suggest that to completely eliminate it, we must look for a treatment that will not only eliminate the rapidly dividing cells, but also target the cancer stem cells that are resistant to conventional treatment.”

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