Concepts of remission, curability and lineage involvement in relationship to the problems of minimal residual leukaemia.
Minimal residual leukaemia (MRL) is due to chemotherapeutic failure. Chemoincurability in chronic myeloid leukaemia and in myelodysplastic syndrome is the norm and is the result of tumour defect arising within the marrow stem cell compartment. We propose that this is indeed the state of affairs in the majority of adult acute leukaemias and such tumours derived from stem cells are chemoincurable. The proportion of acute leukaemias which belong to this category can only be cured by allogeneic bone marrow transplantation though conventional chemotherapy and autotransplant may result in prolonged periods of remission and a return to a preleukaemic state in some patients. A proportion of the acute leukaemias occurring predominantly in children are presently curable by chemotherapy. It is hypothesized that these chemocurable leukaemias derive from the compartment of haemopoietic progenitors already irreversibly committed to a single lineage. Some recent studies using markers of the leukaemic clone to determine the origin of in vitro myeloid colony forming cells support this concept. Intrinsic and/or acquired genetic chemoresistance represents a supplementary restriction to the chemocurability of acute leukaemias. New methods of detecting MRL are sensitive enough to detect up to one leukaemic cell in 10(6) bone marrow mononuclear cells. However, it is possible that even such sensitive techniques will not be sufficient to determine whether patients in complete remission continue to harbour leukaemic cells in the stem cell compartment when the marker of interest might not be expressed.(ABSTRACT TRUNCATED AT 250 WORDS)
Jasmin
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C
Charpentier
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Marion
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Proctor
S J
SJ
D000818:Animals; D004351:Drug Resistance; D006412:Hematopoietic Stem Cells / Q000473:pathology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000473:pathology; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy / Q000473:pathology; D012074:Remission Induction