Effects of chemotherapy on bone marrow stroma in mice with acute myelogenous leukemia. Correlation with CFU-C and CFU-D.
This study describes changes in bone marrow stroma in murine acute myelogenous leukemia (AML). The AML was induced in C57B1 mice by intravenous (i.v.) transfusion of C4198 myelogenous leukemic cells. In untreated leukemic mice, the colony-forming unit fibroblasts (CFU-F) were severely inhibited. In leukemic mice treated by three chemotherapy protocols of cytosine-arabinoside (Ara-C) and adriamycin there was a 200% increase in the life span as compared to untreated leukemic animals and marked reduction of marrow leukemic load. In these mice the stromal inhibition was temporarily relieved, expressed by peaks of CFU-F2-3 days following each protocol. In between the peaks, CFU-F decreased to subnormal levels, remaining low to the end of the disease. In normal mice administered a similar chemotherapy regimen, there were peaks of CFU-F activation after each protocol and normal levels in between the peaks. Granulocyte/macrophage progenitors (CFU-C) of leukemic-treated and normal-treated mice showed increased levels following each chemotherapy protocol. Whereas CFU-C decreased below normal levels in leukemic mice towards the end of the disease, the level of these progenitors remained high in normal mice receiving Ara-C and adriamycin. Colony-forming units in diffusion chamber (CFU-D) showed mild fluctuations in both leukemic and normal mice receiving three protocols of Ara-C and adriamycin. It is possible that despite treatment, the bone marrow stroma in leukemia becomes irreversibly deficient towards the end of the disease and cannot support the residual normal hematopoiesis.
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003561:Cytarabine / Q000009:adverse effects / Q000627:therapeutic use; D004058:Diffusion; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use; D005347:Fibroblasts / Q000166:cytology; D006098:Granulocytes / Q000166:cytology; D006412:Hematopoietic Stem Cells / Q000187:drug effects*; D006918:Hydroxyurea / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000188:drug therapy*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D008264:Macrophages / Q000166:cytology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
D000970:Antineoplastic Agents; D003561:Cytarabine; D004317:Doxorubicin; D006918:Hydroxyurea