Differential expression of the novel oncogene, SALL4, in lymphoma, plasma cell myeloma, and acute lymphoblastic leukemia.
SALL4, a newly identified zinc-finger transcriptional factor important for embryonic development, is mapped to chromosome 20q13. Previously, we reported that SALL4 was constitutively expressed in acute myeloid leukemia and SALL4 transgenic mice developed acute myeloid leukemia. In this study, we aimed to survey SALL4 protein expression in benign and neoplastic hematopoietic tissues in addition to acute myeloid leukemia using immunostaining with a polyclonal anti-SALL4 antibody. Primary hematological tumors (178) and 15 benign hematopoietic tissues were examined. Reverse transcription-polymerase chain reaction was also performed to detect SALL4 mRNA expression on eight precursor B-cell lymphoblastic leukemia/lymphomas, 10 benign hematopoietic tissues, and seven hematopoietic cancer cell lines. Of the benign tissues, SALL4 expression was detectable only in CD34+ hematopoietic stem/progenitor cells (2/2 at protein level, 3/3 at RNA level). In neoplastic tissues, only precursor B-cell lymphoblastic leukemia/lymphomas had detectable SALL4 (12/16 at protein level, 7/8 at RNA level), similar to that observed in acute myeloid leukemia. Of the seven cell lines examined, only those derived from acute myeloid leukemia and precursor B-cell lymphoblastic leukemia/lymphomas were positive. To conclude, SALL4 expression is normally restricted to CD34+ hematopoietic stem/progenitor cells. The persistence of SALL4 expression in leukemic blasts in precursor B-cell lymphoblastic leukemia/lymphomas resembles to what we observed in acute myeloid leukemia, and correlates with the maturation arrest of these cells. We have shown in our previous study that the constitutive expression of SALL4 in mice can lead to acute myeloid leukemia development. The similar expression pattern of SALL4 in acute myeloid leukemia and B-cell lymphoblastic leukemia/lymphomas suggests that these two disease entities may share similar biological features and/or mechanisms of leukemogenesis. More definite studies to investigate the role of SALL4 in the pathogenesis of B-cell lymphoblastic leukemia/lymphomas are needed in the future to address this question.
Cui
Wei
W
Department of Pathology, Joint Program in Transfusion Medicine, Brigham and Women's Hospital/Children's Hospital Boston, Harvard Medical School, Boston, MA 02115, USA.
Kong
Nikki R
NR
Ma
Yupo
Y
Amin
Hesham M
HM
Lai
Raymond
R
Chai
Li
L
D018952:Antigens, CD34 / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D002469:Cell Separation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008223:Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010954:Plasmacytoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
D018952:Antigens, CD34; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; C472575:SALL4 protein, human; D014157:Transcription Factors