Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study aimed to evaluate the effect of melphalan on both terminal divisions and self-renewal capacity of acute myeloblastic leukemia (AML) progenitors (colony-forming units, CFU-L) grown in methylcellulose. Terminal divisions and self-renewal were assayed by primary (PE1) and secondary (PE2) colony formation, respectively. Thirteen cases of AML, were tested. Melphalan induced a negative exponential dose-effect on CFU-L survival. Moreover, melphalan was equally effective in inhibiting CFU-L growth in both PE1 and PE2 assays, with D10 values of 1.53 +/- 0.17 micrograms/ml and 1.59 +/- 0.21 micrograms/ml for PE1 and PE2, respectively (p = 0.48). Cytotoxicity of melphalan on CFU-L did not differ significantly from that observed for normal hemopoietic granulocyte-macrophage colony-forming units, erythroid burst-forming units, and granulocyte-erythroid-macrophage-megakaryocyte progenitors. Mafosfamide-lysine, a stable cyclophosphamide congener, strongly inhibited primary colony formation (PE1) with a D10 value of 14.46 +/- 1.76 micrograms/ml, but was much less efficient in the PE2 assay. Our findings suggest that the self-renewal capacity of AML progenitors can be differentially affected by alkylating agents. Moreover, since it is now considered that chemotherapy should be preferentially directed against the self-renewal of leukemic progenitors, melphalan might offer a greater potential than cyclophosphamide or cyclophosphamide derivatives in the therapy of AML.
Leukemia 1992 Mar
PMID:Effect of melphalan against self-renewal capacity of leukemic progenitors in acute myeloblastic leukemia. 156 57

The effects of human recombinant tumor necrosis factor type alpha (rTNF alpha) on the blast progenitors from 14 acute myeloblastic leukemia (AML) patients and 1 chronic myelogenous leukemia patient in blastic crisis were studied in methylcellulose and suspension cultures. Blast progenitors renew themselves and/or undergo terminal divisions. Plating efficiency of primary colony formation (PE1) in methylcellulose, which is considered to reflect the terminal divisions of blast progenitors, was suppressed by rTFN alpha in a dose-dependent manner in all cases. Plating efficiency of secondary colony formation (PE2) and the recovery of clonogenic cells in suspension culture, which are considered to reflect the self-renewal capacity of blast progenitors, were also suppressed by rTNF alpha in a dose-dependent manner in almost all cases. rTNF alpha also inhibited both PE2 and clonogenic cells in suspension culture, even in relapsed AML patients who were very refractory to intensive chemotherapies. The results demonstrate that rTNF alpha inhibits not only terminal divisions but also the self-renewal capacity of leukemic blast progenitors. The finding that rTNF alpha suppressed the self-renewal capacity of leukemic blast progenitors proposes the utility of rTNF alpha to AML therapy.
Leukemia 1989 Sep
PMID:Effects of recombinant human tumor necrosis factor on the self-renewal capacity of leukemia blast progenitors in acute myeloblastic leukemia. 276 17

The sensitivity to cytosine arabinoside (Ara-C) of blast progenitors from 22 acute myeloblastic leukaemia (AML) patients was studied in methylcellulose and suspension cultures. Primary colony-formation (PE1) in methylcellulose reflects the terminal divisions of blast progenitors, while secondary colony formation (PE2) in methylcellulose and the clonogenic cells recovery in suspension are considered to be based on the self-renewal of blast progenitors. In any patient, PE2 or clonogenic cells in suspension were more sensitive to Ara-C than PE1. The results indicate that Ara-C effectively suppresses not only terminal divisions but also self-renewal of blast progenitors D10 Ara-C value, the dose required to reduce survival to 10% of control, for PE1, PE2 and clonogenic cells in suspension showed marked patient-to-patient variation. No significant correlation was found between D10 Ara-C in methylcellulose or suspension culture and the response to treatment with a combination chemotherapy of 6-mercaptopurine, Ara-C and daunorubicin. However, a relapsed patient whose D10 values in methylcellulose and suspension cultures were very high showed poor response to a high-dose Ara-C protocol, where Ara-C was given alone at a high dose. The application of chemosensitivity test as a prediction of the clinical outcome may be dependent on the treatment protocol.
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PMID:Relationship between the in vitro sensitivity to cytosine arabinoside of blast progenitors and the outcome of treatment in acute myeloblastic leukaemia patients. 319 Oct 30