Leukemia translocations

Chronic myelogenous leukemia Translocation BCR-ABL BCR-ABL (tyrosine-kinase activity) Imatinib, Dasatinib, Nilotinib, Bosutinib... 

Acute promyelocytic leukemia Translocation PML/RARA PML/RARA All-frans retinoic acid, arsenic trioxide... 

The presence of chromosomal translocations is a consistent feature of many leukemia s, lymphomas, and certain solid tumors. At the genetic level, these events can either deregulate an intact gene by disruption or removal and replacement of the adjacent controlling elements, or create a new fusion gene that express the N-terminus of one protein fused to the C-terminus of another protein. 

Inhibition of hematopoietic growth factors Imatinib (Glivec ) is applied to treat chronic myeloid leukemia in Philadelphia-chromosome positive patients. In these patients, translocation of parts of chromosomes 9 and 22 results in the expression of a fusion protein with increased tyrosine kinase activity, called Bcr-Abl. Imatinib is a small Mw inhibitor selective for the tyrosine kinase activity of Bcr-Abl. Thereby, it inhibits the Bcr-Abl induced cell cycle progression and the uncontrolled proliferation of tumor cells. 

For patients with myelodysplastic syndrome or AML as a secondary neoplasm, there are a number of key features characteristic of the leukemia. Alkylator-related secondary leukemias after Hodgkin s disease usually have a myelodysplastic prodrome and a monosomy 5 or monosomy 7. Secondary ANLL with the use of epipodophyllotoxin (etoposide) demonstrates mainly M4 or M5 morphology and exhibits translocations within the MLL gene with 1 lq23 chromosomal alterations.8... 

O A chromosomal translocation, the Philadelphia chromosome, is responsible for chronic myelogenous leukemia (CML). 

Brock, T. G., McGish, R. W. and Peters-Golden, M. Translocation and leukotriene synthetic capacity of nuclear 5-lipoxygenase in rat basophilic leukemia cells and alveolar macrophages. /. Biol. Chem. 270 21652-21658,1995. 

A well-known use of molecular methods is in the study of chromosomal translocations. Thus, in Philadelphia chromosome (ph1) positive chronic myelogenous leukemia (CML), the C-abl oncogene on chromosome 9 is translocated to a region on chromosome 22 called the breakpoint cluster region, or bcr. This (t9 22) translocation results in production of an abnormal fusion protein... 

Chronic myeloid leukemia (CML) occurs when there is a translocation of chromosomes 9 and 22 (also called Philadelphia translocation—a chromosomal abnormality). These two different chromosomes break off and reattach on the opposite chromosome. A consequence is that the activity of the Bcr-Abl gene, which encodes the enzyme tyrosine kinase, is turned on all the time. With this heightened activity, high levels of white blood cells are produced in the bone marrow. 

Crowley JA, Wang Y, Rapoport AP, Ning Y (2005) Detection of MOZ-CBP fusion in acute myeloid leukemia with 8 16 translocation. Leukemia 19 2344-2345 Dash A, Gilliland DG (2001) Molecular genetics of acute myeloid leukaemia. Best Pract Res Clin Haematol 14 49-64... 

Rozman M, Camos M, Colomer D, Villamor N, Esteve J, Costa D, Carrio A, Aymerich M, Aguilar JL, Domingo A, Sole F, Gomis F, Florensa L, Montserrat E, Campo E (2004) Type I MOZICBP (MYST31CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8 16)(pll pl3) translocation. Genes Chromosomes. Cancer 40 140-145 Rubinstein JH, Taybi H (1963) Broad thumbs and toes and facial abnormalities. Am J Dis Child 105 588-608... 

MYST family HATs frequently fused to other proteins as a result of chromosomal translocation in acute myeloid leukemia. 

Kitabayashi 1, Aikawa Y, Nguyen LA, Yokoyama A, Ohki M (2001a) Activation of AMLl-mediated transcription by MOZ and inhibition by the MOZ-CBP fusion protein. Embo J 20 7184-7196 Kitabayashi 1, Aikawa Y, Yokoyama A, Hosoda F, Nagai M, Kakazu N, Abe T, Ohki M (2001b) Fusion of MOZ and p300 histone acetyltransferases in acute monocytic leukemia with a t(8 22)(pll ql3) chromosome translocation. Leukemia 15 89-94... 

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