SSBP2, a candidate tumor suppressor gene, induces growth arrest and differentiation of myeloid leukemia cells.
Acute myelogenous leukemia (AML) is the most common leukemia in adults with clonal proliferation of myeloid stem cells. Two or more cooperating mechanisms, namely block in differentiation, enhanced proliferation and resistance to programmed cell death, underlie this neoplastic transformation. Nonrandom, complete and partial deletions of chromosome 5 are common anomalies in AML. Using positional cloning strategies, we characterized an evolutionarily conserved candidate myeloid leukemia suppressor gene encoding sequence-specific single-stranded DNA binding protein 2 (SSBP2) from chromosome 5q13.3, a locus that is frequently deleted in AML. Recent studies in Drosophila and Xenopus demonstrate a pivotal role for SSBPs in embryonic differentiation. In mammals, SSBP2 is one of three highly related and ubiquitously expressed genes. Here, we identify frequent loss of SSBP2 protein expression in human AML cell lines using highly specific antibodies. Furthermore, inducible expression of SSBP2 in the AML cell line U937 leads to loss of clonogenicity, G1 arrest and partial differentiation. Remarkably, inducible expression of SSBP2 is accompanied by downregulation of C-MYC expression. Our findings are consistent with human SSBP2 being a novel regulator of hematopoietic growth and differentiation, whose loss confers a block in differentiation advantage to myeloid leukemic cells.
Liang
Hong
H
Department of Molecular Genetics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Box 45, Houston, TX 77030, USA.
Samanta
Susmita
S
Nagarajan
Lalitha
L
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D049109:Cell Proliferation; D002522:Chlorocebus aethiops; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D016193:G1 Phase / Q000187:drug effects; D005786:Gene Expression Regulation; D016147:Genes, Tumor Suppressor; D016259:Genes, myc / Q000187:drug effects; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D020298:U937 Cells
D004268:DNA-Binding Proteins; C477058:SSBP2 protein, human