Clustered immature myeloid precursors in intertrabecular region during remission evolve from leukemia stem cell near endosteum and contribute to disease relapse in acute myeloid leukemia

Abstract

Most acute myeloid leukemia (AML) cannot be cured because leukemia stem cells (LSC) will contribute to eventual relapse. However, how LSC initiate relapse is not yet fully understood. We performed a retrospective study on bone marrow sections from AML patients during complete remission (CR), demonstrating that single and double immature myeloid precursors were located near endosteum and clustered precursors (≥ 3 cells/group) in intertrabecular region. Based on our observations, we hypothesize that after retrieval of myelotoxic regimen, LSC harboring near endosteum divide and differentiate into progeny cells which proliferate and then form colony clusters. Meanwhile, these clusters may migrate to intertrabecular region under the actions of cell migration factors. Without any interventions, clustered immature myeloid precursors may proliferate and hematologic relapse is then unavoidable.