Cloning, expression, and characterization of a cDNA encoding a novel human growth factor for primitive hematopoietic progenitor cells

Abstract

Multiple growth factors synergistically stimulate proliferation of primitive hematopoietic progenitor cells. A human myeloid cell line, KPB-M15, constitutively produces a novel hematopoietic cytokine, termed stem cell growth factor (SCGF), possessing species-specific proliferative activities. Here we report the molecular cloning, expression, and characterization of a cDNA encoding human SCGF using a newly developed SHDM vector that is more efficient for differential and expression cloning. cDNA for SCGF encodes a 29-kDa polypeptide without N-linked glycosylation. SCGF transiently produced by COS-1 cells supports growth of hematopoietic progenitor cells through a short-term liquid culture of bone marrow cells and exhibits promoting activities on erythroid and granulocyte͞macrophage progenitor cells in primary semisolid culture with erythropoietin and granulocyte͞ macrophage colony-stimulating factor, respectively. Expression of SCGF mRNA is restricted to myeloid cells and fibroblasts, suggesting that SCGF is a growth factor functioning within the hematopoietic microenvironment. SCGF could disclose some human-specific mechanisms as yet unidentified from studies on the murine hematopoietic system.

Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study

“…Stem-cell growth factor (SCGF) is a member of the C-type lectin superfamily and is a novel human growth factor that supports growth of primitive hematopoietic progenitor cells. 21,26 SCGF was another gene which was significantly overexpressed at relapse. Some of the genes down-regulated at relapse compared with initial diagnosis included proapoptotic genes (Harakiri), antiproliferative genes (BTG1 and BTG2) and a putative tumor suppressor (BCL7A).…”

“…These 19 relapse samples were randomly selected from the cohort of 60 patients treated at relapse in COG AALL01P2 but did not include the relapse samples from the 35 pairs. We selected those genes implicated previously in transformation as well as those that might be suitable targets for future therapeutic modulation, such as BIRC5, 16 PTTG1, 17,18 TOP2A, 19 CCNB1, 20 SCGF, 21 and BCL7A 22 for validation. Although some of these genes were not included in the top 20 gene list, all genes were significantly differentially expressed (P Ͻ .005; see gene list in Table S3B).…”

A Novel Functional Variant in the Stem Cell Growth Factor Promoter Protects against Severe Malarial Anemia

“…Human SCGF cDNA encodes a 29-kDa polypeptide (15) for which there are currently two known isoforms: SCGF-␣, a 323-amino-acid protein; and SCGF-␤, a 245-amino-acid protein formed from cleavage of the conserved carbohydrate domain (30). In individuals undergoing stem cell transplantation, elevated serum SCGF levels are associated with enhanced hematopoietic recovery (17).…”

Serum stem cell growth factor for monitoring hematopoietic recovery following stem cell transplantation

“…1 It was detected in the cultured supernatant of KPB-M15 cells, a human myeloid cell line established from a patient with chronic myeloid leukemia in blast crisis. 2 The cDNA for SCGF encodes a 29-kDa polypeptide without N-linked glycosylation, which belongs to the C-type lectin superfamily.…”

“…BM mononuclear cells were also separated into CD34 + and CD34 À cells using an immunomagnetic bead system (MACS, Miltenyi Biotec, Glodbach, Germany The CFU-C assay was performed as described previously 1 . All cultures were done in triplicate, and the number of CFU-C was scored at day 10 of culture.…”