Linking miRNA regulation to BCR-ABL expression: the next dimension.
The introduction of tyrosine kinase inhibitors in the treatment of BCR-ABL1-rearranged malignancies has revolutionized therapy, but the prognosis for acute leukemias remains suboptimal. In this issue of Cancer Cell, Bueno et al. (2008) add a new dimension to the regulation of ABL1 expression. The authors demonstrate that ABL1 is a direct target of miR-203, miR-203 is silenced by genetic and epigenetic mechanisms in hematopoietic malignancies expressing either ABL1 or BCR-ABL1, and restoration of miR-203 expression reduces ABL1 and BCR-ABL1 levels and inhibits cell proliferation. These findings may have broad implications for mechanisms underlying malignant transformation in hematopoietic and other malignancies.
Division of Hematology/Oncology, Children's Hospital Boston, Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Harvard Medical School, Boston, MA 02115, USA.
Jörg
J
Faber
Richard I
RI
Gregory
Scott A
SA
Armstrong
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019175:DNA Methylation; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism*; D015854:Up-Regulation
D000970:Antineoplastic Agents; D035683:MicroRNAs; D047428:Protein Kinase Inhibitors; C406060:abl-bcr fusion protein, human; D016044:Fusion Proteins, bcr-abl; D016315:Proto-Oncogene Proteins c-abl