title: Differential response to stem cell factor and Flt3 ligand by the FAB subtype in acute myeloid leukemia clonogenic cells.
abstract: Proliferative response of blast clonogenic cells to various hematopoietic growth factors (HGF), including stem cell factor (SCF) and flt3 ligand (FL) was investigated in 100 patients with acute myeloid leukemia (AML) and chronic myelogenous leukemia (CML) in myeloid crisis (MC). The frequency of spontaneous colony formation was significantly high in CML in MC (55%) and AML French-American-British (FAB) subtype M4 (48%) compared with M2 (16%). No spontaneous colony was formed in any of the patients with M1 and M3. The frequency of proliferative response to various HGF alone and in combination according to FAB subtype and CML in MC was as follows: that to granulocyte colony-stimulating factor (G-CSF) was lowest in M1 and CML in MC (50%) compared with other FAB subtypes (>or=86%), that to granulocyte-macrophage CSF (GM-CSF) was lowest in CML in MC (44%) compared with FAB subtypes (>or=74%), and that to interleukin-3 (IL-3) was lowest in CML in MC (30%) compared with FAB subtypes (>or=78%). SCF and FL stimulated blast colony formation in 11% and 17% of patients with M3, respectively, but there was no response to both, and in 60% and 57% of patients with CML in MC, respectively, with 14% showing a response to both. The frequency of proliferative response to both SCF and FL increased in the order of M1 (33%), M2 (63%), M4-5 (95%), and M6 (100%). The results are summarized as follows: absence of spontaneous colony formation and response to HGF other than SCF and FL, designated as HGF-dependent growth (M3); spontaneous colony formation and lowest response to HGF, designated as autonomous growth (CML in MC); and spontaneous colony formation and highest response to HGF including SCF and FL, designated as autocrine growth (M4-6). M1 and M2 were intermediate between CML in MC and M4-6. The relation between in vitro growth pattern of blast clonogenic cells and prognosis in AML FAB subtype and CML in MC is discussed.
authors.affiliation: First Department of Internal Medicine, Saitama Medical School, Saitama, 350-0451, Japan. murohashi-ikuo@spu.ac.jp
authors.forename: Ikuo
authors.initials: I
authors.lastname: Murohashi
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Yoshida
authors.forename: Kuniya
authors.initials: K
authors.lastname: Kishimoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Takahashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Wakao
authors.forename: Itsuro
authors.initials: I
authors.lastname: Jinnai
authors.forename: Fumiharu
authors.initials: F
authors.lastname: Yagasaki
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Kawai
authors.forename: Toshiya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Akira
authors.initials: A
authors.lastname: Matsuda
authors.forename: Kunitake
authors.initials: K
authors.lastname: Hirashima
authors.forename: Masami
authors.initials: M
authors.lastname: Bessho
mesh_terms: D000208:Acute Disease; D001752:Blast Crisis / Q000188:drug therapy / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000473:pathology; D007951:Leukemia, Myeloid / Q000188:drug therapy* / Q000473:pathology; D015479:Leukemia, Myelomonocytic, Acute / Q000188:drug therapy* / Q000473:pathology; D008565:Membrane Proteins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D012189:Retrospective Studies; D019089:Stem Cell Factor / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007377:Interleukin-3; D008565:Membrane Proteins; D011994:Recombinant Proteins; D019089:Stem Cell Factor; D014409:Tumor Necrosis Factor-alpha; C084881:flt3 ligand protein; D016179:Granulocyte Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor