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Relapse after allogeneic BMT for chronic myeloid leukemia (CML) may be sustained by a small number of leukemic ‘stem cells’: a hypothesis

Abstract

‘. . . .the leukemic stem line is a small minority within the total cell mass; . . . . when the leukemic stem line is not exceeding the normal stem cell numbers, its proliferation may still be under partial control. . . .’ LG Lajtha, Blood Cells 1981; 7 : 45–62

We performed cytogenetic analysis on fresh bone marrow cells and on progenitor cell colonies in a patient who relapsed after allogeneic BMT for CML and was subsequently treated with donor lymphocyte infusions (DLI). Two Philadelphia-positive clones were identified at relapse. One clone displayed an additional chromosomal abnormality most likely induced by radio-chemotherapy and therefore arising in a single cell. This cell displays the characteristics of a stem cell, since it was able to support 20% of Ph-positive hemopoiesis for 5 months. If the progeny of a single Ph-positive stem cell account for 20% of hemopoiesis, a very low number of leukemic stem cells may sustain relapse after allogeneic BMT. This is in keeping with two observations: (1) at relapse, long-term culture initiating cells (LTC-IC) were all donor-derived and Ph-negative; (2) on average, the pace of the disease is very slow after relapse following allogeneic-BMT. Therefore, we hypothesize that a small number of leukemic stem cells may be involved in the initial events of relapse following BMT for CML.

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Frassoni, F., Podestà, M., Piaggio, G. et al. Relapse after allogeneic BMT for chronic myeloid leukemia (CML) may be sustained by a small number of leukemic ‘stem cells’: a hypothesis. Bone Marrow Transplant 24, 689–691 (1999). https://doi.org/10.1038/sj.bmt.1701951

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