Identification and functional characterization of the novel acute monocytic leukemia associated antigen MLAA-34.
We have previously applied the method of serologic analysis of recombinant cDNA expression library (SEREX) on acute monocytic leukemia to identify monocytic leukemia-associated antigens. Using this approach, we identified a novel gene, MLAA-34, which exclusively reacted with sera from allogeneic leukemia patients but not with normal donor sera. Here, we further characterized its gene structure and explored the function. We first determined both 5' and 3' end by RLM-RACE and cloned full-length cDNA of MLAA-34 in U937 cell line. Analysis of full cDNA sequence showed that MLAA-34 is highly homologous to known human gene CAB39L, but differs from two transcript splice variants of CAB39L. Thus, we propose that MLAA-34 is a novel CAB39L's splice variant associated with acute monocytic leukemia. Because the functions of MLAA-34 and CAB39L are both very unclear, then we investigated the role of MLAA-34 in U937 cell line using RNA interference technology. The results showed that the downregulation of MLAA-34 expression significantly suppressed the proliferation of U937 cells in vitro, and increased the spontaneous apoptosis of these leukemia cells. All these data indicated that MLAA-34 may be a novel anti-apoptotic factor related closely to carcinogenesis or progression of acute monocytic leukemia. The anti-apoptotic pathways of MLAA-34 remain further exploration. This study warrants further investigations to verify MLAA-34 as a promising antigen and a molecular target for therapeutic applications in acute monocytic leukemia.
Zhang
Peng-Yu
PY
Department of Clinical Hematology, Affiliated No. 2 Hospital, Xi'an Jiaotong University School of Medicine, The west five road, 157#, 710004, Xi'an, Shaanxi, China.
Zhang
Wang-Gang
WG
He
Ai-Li
AL
Wang
Jian-Li
JL
Li
Wen-Bin
WB
D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000235:genetics* / Q000276:immunology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005434:Flow Cytometry; D015723:Gene Library; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D020298:U937 Cells
D000951:Antigens, Neoplasm; D051017:Apoptosis Regulatory Proteins; C534238:CAB39L protein, human