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)

In view of the elevated risk of leukemia among A-bomb survivors, genetic alterations associated with Leukemia can be considered to have been induced by ionizing radiation. Therefore, to clarify this possibility, an examination was made to see whether genetic changes such as BCR-ABL translocation closely associated with chronic myelogenous leukemia (CML) are actually induced by radiation. BCR-ABL translocation is easily detected by means of reverse transcription polymerase chain reaction. One hundred million cells of the promyelocytic leukemia-derived cell line HL60, which do not have such a gene rearrangement, were irradiated with 100 Gy of X-ray, after which RNA was extracted and examined for any rearrangements of BCR and ABL genes. Five kinds of bands were observed in the HL60 cells irradiated with 100 Gy of X-ray, and it became clear that these positive bands contain both BCR gene and ABL gene by the direct sequencing method. Furthermore, these gene rearrangements included not only the rearrangements specifically identified with CML but also atypical rearrangements which are not generally observed clinically. The induction by X-irradiation of such gene changes characteristic of malignant tumors, which are closely associated with radiation carcinogenesis, suggests that they are the initial gene changes in radiation carcinogenesis.
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PMID:[Gene rearrangement and radiation carcinogenesis]. 802 92

Ionizing radiation is a well-known risk factor of cancer development, but the mechanism of radiation induced carcinogenesis is not clear. Chromosomal rearrangements induced by radiation most likely are one of the principal genetic alterations resulting in malignant transformation. The chimeric BCR-ABL associated with chronic myelogenous leukemia (CML) and H4-RET oncogenes associated with thyroid papillary carcinoma are the result of a translocation and inversion, respectively. In vitro studies showed these genes were induced by high-doses of X-irradiation in cell lines. Studies also show that therapeutic external X-ray doses as high as 60 Gy for treatment of various childhood cancers including Hodgkin's disease significantly increase the risk of thyroid cancer. Therefore, we examined the induction and persistence of these chimeric genes in human thyroid tissues transplanted in scid mice after 50 Gy exposure as a function of time for 2 months to elucidate the early events of thyroid carcinogenesis. The H4-RET genes were detected on day 2 and throughout the 2 month period. On the other hand, BCR-ABL genes were detected on day 2 and were undetectable subsequently. These results suggest that ionizing radiation causes various oncogene activations, but cells with only specific gene alteration uniquely associated with thyroid carcinogenesis are selectively retained demonstrating one of the early events in the beginnings of radiation carcinogenesis in human thyroid tissues.
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PMID:Continued expression of a tissue specific activated oncogene in the early steps of radiation-induced human thyroid carcinogenesis. 933 21