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. 1999 Sep;24(6):689-91. doi: 10.1038/sj.bmt.1701951.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow Transplantation*
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / therapy*
  • Lymphocyte Transfusion
  • Neoplastic Stem Cells / pathology*
  • Recurrence
  • Transplantation, Homologous