Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Ikaros gene is required for normal development of lymphocytes and frequent intragenic deletions of Ikaros have been identified in acute lymphoblastic leukemia. However, little is known about the role of Ikaros in myeloid malignancies. Here we discuss the role of Ikaros as a lineage master regulator during the onset and progression of myeloid leukemias, namely CALM-AF10 positive acute myeloid leukemia and chronic myeloid leukemia. Alterations of Ikaros at the gene or protein level may act as a bi-directional lineage switch subverting developmental plasticity for malignant transformation. Finally, we propose that promiscuous signaling involving Ikaros and FOXO transcription factors might be a critical link between early lineage fate and uncontrolled proliferation.
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PMID:Up a lymphoid blind alley: Does CALM/AF10 disturb Ikaros during leukemogenesis? 2176 76

The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294-335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6.
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PMID:FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia. 2282 78