Long-Term Marrow Culture Reveals Chromosomally Normal Hematopoietic Progenitor Cells in Patients with Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia

Abstract

We found that when marrow cells from four patients with newly diagnosed Philadelphia chromosome-positive chronic myelogenous leukemia were maintained in culture for two to four weeks, a previously undetectable population of chromosomally normal hematopoietic cells (including erythroid, granulopoietic, and pluripotent progenitors) became readily demonstrable in three cases. Time-course studies showed that in such cultures the dominant Philadelphia chromosome-positive population rapidly disappeared, in contrast to coexisting chromosomally normal progenitors, which remained detectable for periods of two to three months. Long-term marrow cultures thus offer a new approach to the assessment of a suppressed but functionally intact population of chromosomally normal hematopoietic stem cells in patients with chronic myelogenous leukemia.

Residual Ph‐negative stem cells in chronic myeloid leukemia‐sometimes or always?

“…This observation must mean that at least in some patients the peripheral blood contains a mixture of Ph-positive and Ph-negative progenitor cells. This conclusion derived further support from data reported by the Vancouver group [14]. They established bone marrow cells from CML patients in Dexter-type long-term culture and demonstrated at least in some cases that Ph-negative BFU-E could be identified early and survived longer than their Ph-positive counterparts.…”

Insights into the stem cells of chronic myeloid leukemia

“…14 Soon after, in the 1980's, we showed that a persisting and functionally intact, but suppressed, residual normal HSC population could be revealed in most patients when this compartment was selectively assessed. 15 These findings encouraged a broader search for therapeutic alternatives to allogeneic bone marrow transplantation that could take advantage of the possibility that these residual autologous HSCs might be sufficient to permanently re-establish normal hematopoiesis. Ultimately, this concept culminated in 'first-in-CML' studies demonstrating that the product of a shared oncogenic mutation could serve as a clinically useful therapeutic target.…”

The Use of Cultured Bone Marrow Cells for Autologous Transplantation in Patients with Acute Myeloblastic Leukemia

“…In cultures of bone marrow cells from untreated patients with chronic granulocytic leukaemia (CML), the Philadelphia chromosome decreased, after being present in over 95% of mitoses, to almost undetectable levels. In the same cultures, Ph-negative cells became the predominant mitotic population [4]. Similarly, in some cultures established from bone marrow from patients with newly diagnosed acute myeloblastic leukaemia (AML) , the size of the leukaemic clone (assessed either by chromosome markers or by a characteristic abnormal growth pattern in colony assays) diminished to undetectable levels, while normal haemopoiesis became dominant ( [5,6] and our unpublished results).…”