Expression and functional analysis of granulocyte colony-stimulating factor receptors on CD34++ cells in patients with myelodysplastic syndrome (MDS) and MDS-acute myeloid leukaemia.
CD34++ cells from 45 patients with myelodysplastic syndrome (MDS) and MDS-acute myeloid leukaemia (MDS-AML) were observed by flow cytometry for the expression of granulocyte colony-stimulating factor receptor (G-CSFR). Ten patients had a significantly reduced expression of G-CSFR. Late stages of disease showed a higher proportion of either high or low G-CSFR expression than earlier stages. In MDS refractory anaemia (RA), G-CSFR was inversely related to CD33 expression. Most patients (9/10) with low G-CSFR expression had neutropenia of the peripheral blood. Neutropenia was less common in the normal group, but also occurred in the high expression group. No neutrophil response was observed following G-CSF administration to MDS-AML patients (6/6) with low G-CSFR expression. In the high expression group, patients (3/3) showed a response to G-CSF while, in the normal group (1/2), the response was minor. In the normal- or high-receptor-expressing groups, the receptors were functionally active in terms of apoptosis but not proliferation and clonogenic growth, although no clear correlation to receptor expression was observed. The G-CSFR signal transduction pathway in the normal and high group was not deficient of messenger RNA for either janus kinases (Jaks) or signal transducers and activators of transcription (Stats). These findings suggest that the lowered expression of G-CSFR may cause neutropenia in MDS and MDS-AML patients and, therefore, may partially explain the neutropenia in myelodysplastic patients.
Sultana
Tanvira Afroze
TA
Department of Hematology and Oncology, Division of Clinical and Experimental Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Harada
Hironori
H
Ito
Kinro
K
Tanaka
Hideo
H
Kyo
Taiichi
T
Kimura
Akiro
A
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000276:immunology*; D017209:Apoptosis; D002455:Cell Division; D002478:Cells, Cultured; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D007951:Leukemia, Myeloid / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000276:immunology*; D009503:Neutropenia / Q000276:immunology; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000032:analysis / Q000378:metabolism*; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology*
D018952:Antigens, CD34; D016188:Receptors, Granulocyte Colony-Stimulating Factor; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor