Cancer Report

Cancer : Chronic myelogenous leukaemia (CML)
Summary
Cancer Name Chronic myelogenous leukaemia (CML)
 
Clinics and Pathology
Disease CML is a malignant chronic myeloproliferative disorder (MPD) of the hematopoietic stem cell.
Epidemiology annual incidence: 10/106 (from 1/106 in childhood to 30/106 after 60 yrs);
median age: 30-60 yrs;
sex ratio: 1.2M/1F
Treatment a IFN therapy or allogeneic bone marrow transplantation (BMT), donor leukocytes infusions
Prognosis median survival: 4 yrs with conventional therapy (hydroxyurea, busulfan), 6 yrs with aIFN therapy; allogeneic bone marrow transplantation may cure the patient; otherwise, the best treatment to date associates interferon a, hydroxyurea and cytarabine
 
Related Genes
Gene Symbol PDGFRA
Description From COSMIC:
 
Gene Symbol VRK1
 
Gene Symbol RPL22
Description From cancer gene census of CGP:
 
Gene Symbol BCR
Description From cancer gene census of CGP: " various splicingsmain form: 160 KDa; N-term Serine-Treonine kinase domain, SH2 binding, and C-term domain which functions as a GTPase activating protein for p21rac; widely expressed; cytoplasmic localisation; protein kinase; probable role in signal transduction "
 
Gene Symbol KIT
Description From COSMIC:
 
Gene Symbol EVI1
Description From cancer gene census of CGP:
 
Gene Symbol PTPN11
 
Gene Symbol ABL1
Description From COSMIC, cancer gene census of CGP
 
Gene Symbol CCDC6
Description From cancer gene census of CGP:
 
Gene Symbol TPR
Description From OMIM: "The TPR locus, which has been mapped to chromosome 1, expresses a 10-kb RNA in all human cell lines tested (Dean et al., 1985). In a cell line rendered tumorigenic with the direct-acting carcinogen N-methyl-N-prime-nitronitrosoguanidine (MNNG), Dean et al. (1987) defined an activated MET oncogene that expresses a novel 5.0-kb RNA transcript which is a hybrid RNA derived from a DNA rearrangement involving the TPR locus and the MET locus (on 7q; 164860). Although most of the hybrid RNA is derived from the MET oncogene, the 5-prime portion uses some exons from the TPR gene, presumably the promoter region. Oncogenic activation of MET is reminiscent of the Philadelphia chromosomal translocation in chronic myeloid leukemia that generates the hybrid BCR/ABL tyrosine kinase p210 (see 151410). Gonzatti-Haces et al. (1988) identified the proteins encoded by the human TPR-MET oncogene and the human MET protooncogene."
 
Gene Symbol MSH6
Description From COSMIC:
 
Gene Symbol GPR156
Description alternate splicing (1a and 1b) in 5'giving rise to 2 proteins of 145 kDa; contains SH (SRC homology) domains; N-term SH3 and SH2 - SH1 (tyrosine kinase) - DNA binding motif - actin binding domain C-term; widely expressed; localisation is mainly nuclear; inhibits cell growth
 
Gene Symbol CDKN2A
Description From COSMIC:
 
Gene Symbol N-RAS
Description From COSMIC:
 
Gene Symbol HOXA11
Description From cancer gene census of CGP:
 
Gene Symbol MSI2
Description From cancer gene census of CGP:
 
Gene Symbol PDGFRB
Description From cancer gene census of CGP:
 
Gene Symbol TOPORS
Description From COSMIC:
 
Gene Symbol K-RAS
Description From COSMIC:
 
Cytogenetics
Cytogenetics Molecular is a useful tool for diagnostic ascertainment in the case of a 'masked Philadelphia' chromosome, where chromosomes 9 and 22 all appear to be normal, but where cryptic insertion of 3' ABL within a chromosome 22 can be demonstrated
 
Bibliography
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Authors Ahmed M, Dusanter-Fourt I, Bernard M, Mayeux P, Hawley RG, Bennardo T, Novault S, Bonnet ML, Gisselbrecht S, Varet B, Turhan AG.
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PubMedID 7993792
 
Title Bcr/Abl expression stimulates integrin function in hematopoietic cell lines.
Authors Bazzoni G, Carlesso N, Griffin JD, Hemler ME.
Citations J Clin Invest 1996; 98: 521-528.
PubMedID 97357243
 
Title Chronic myelogenous leukemia.
Authors Enright H, McGlave PB
Citations Curr Opin Hematol. 1995; 2: 293-299. Review.
PubMedID 97196352
 
Title Chronic myelogenous leukemia: biology and therapy
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PubMedID 93218288
 
Title Complex translocations, simple variant translocations and Ph-negative cases in chronic myelogenous leukaemia.
Authors Huret JL.
Citations Hum Genet. 1990; 85: 565-568. Review
PubMedID 91033796
 
Title Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia.
Authors Oda T, Heaney C, Hagopian JR, Okuda K, Griffin JD, Druker BJ.
Citations J Biol Chem 1994; 269: :22925-22928.
PubMedID 98039279
 
Title Interferon alfa-2b combined with cytarabine versus interferon alone in chronic myelogenous leukemia. French Chronic Myeloid Leukemia Study Group
Authors Guilhot F, Chastang C, Michallet M, Guerci A, Harousseau JL, Maloisel F, Bouabdallah R, Guyotat D, Cheron N, Nicolini F, Abgrall JF, Tanzer J
Citations N Engl J Med. 1997; 337: 223-229.
PubMedID 98039279
 
Title Molecular insights into the Philadelphia translocation.
Authors Heisterkamp N, Groffen J.
Citations Hematol Pathol. 1991; 5: 1-10. Review.
PubMedID 91267879
 
Title Oncogenic Abl and Src tyrosine kinases elicit the ubiquitin-dependent degradation of target proteins through a Ras-independent pathway.
Authors Dai Z, Quackenbush RC, Courtney KD, Grove M, Cortez D, Reuther GW, Pendergast AM.
Citations Genes Dev 1998; 12: 1415-1424.
PubMedID 91267879
 
Title P210 and P190(BCR/ABL) induce the tyrosine phosphorylation and DNA binding activity of multiple specific STAT family members.
Authors Ilaria RL Jr, Van Etten RA.
Citations J Biol Chem 1996; 271: 31704-31710.
PubMedID 91267879
 
Title Philadelphia-negative (Ph-) chronic myeloid leukemia (CML): comparison with Ph+ CML and chronic myelomonocytic leukemia. The Groupe Francais de Cytogenetique Hematologique.
Authors Martiat P, Michaux JL, Rodhain J.
Citations Blood. 1991; 78: 205-112.
PubMedID 91300057
 
Title Prognostic implications of differences in telomere length between normal and malignant cells from patients with chronic myeloid leukemia measured by flow cytometry.
Authors Brummendorf TH, Holyoake TL, Rufer N, Barnett MJ, Schulzer M, Eaves CJ, Eaves AC, Lansdorp PM.
Citations Blood 2000; 95:1883-1890.
PubMedID 91300057
 
Title Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia.
Authors Sokal JE, Gomez GA, Baccarani M, Tura S, ClarksonBD, Cervantes F, Rozman C, Carbonell F, Anger B, Heimpel H, et al.
Citations Blood. 1988; 72: 294-298.
PubMedID 88269833
 
Title Protein tyrosine phosphatase 1B antagonizes signalling by oncoprotein tyrosine kinase p210 bcr-abl in vivo.
Authors LaMontagne KR Jr, Flint AJ, Franza BR Jr, Pandergast AM, Tonks NK.
Citations Mol Cell Biol 1998; 18:2965-2975.
PubMedID 88269833
 
Title Transformation of hematopoietic cells by BCR/ABL requires activation of a PI-3k/Akt-dependent pathway.
Authors Skorski T, Bellacosa A, Nieborowska-Skorska M, Majewski M, Martinez R, Choi JK, Trotta R, Wlodarski P, Perrotti D, Chan TO, Wasik MA, Tsichlis PN, Calabretta B.
Citations EMBO J 1997; 16: 6151-6161.
PubMedID 92031068
 
Title The molecular pathology of chronic myelogenous leukaemia.
Authors Kurzrock R, Talpaz M.
Citations Br J Haematol. 1991;79 Suppl 1: 34-37. Review.
PubMedID 92031068
 
Title The function of BCR/ABL and related proto-oncogenes.
Authors Gotoh A, Broxmeyer HE.
Citations Curr Opin Hematol. 1997; 4: 3-11. Review.
PubMedID 88269833
 
Source and Citation
Source Atlas of Genetics and Cytogenetics in Oncology and Haematology
Citation Huret JL . Chronic myelogenous leukaemia (CML). Atlas Genet Cytogenet Oncol Haematol. December 1997 .
URL : http://AtlasGeneticsOncology.org/Anomalies/CML.html
URL http://AtlasGeneticsOncology.org/Anomalies/CML.html