chronic myeloid leukemia

Digital slides

 UI:483 - Chronic myelogenous leukemia

Evolution

 acute leukemias

• acute erythroid leukemia

Cytogenetics

Most patients with chronic myelogenous leukemia (CML) show a Philadelphia (Ph) chromosome with a characteristic translocation between chromosomes 9 and 22.

There are variant complex translocations involving other chromosomes in addition to the standard translocation:
 t(4;12;7;9;22) (18474301)

Molecular biology

 BCR-ABL fusion protein expression by t(9;22)

CGH (17696194, 16425296)

 chromosomal losses

• 1p36 loss (17696194)
• 2q26.2-q37.3 loss (16425296)
• 5q21 loss (17696194)
• 5q23.1-q23.3 loss (16425296)
• 5q31.2-q32 loss (16425296)
• 7p21.3-p11.2 loss (16425296)
• 7q31.1-q31.33 loss (16425296)
• 8pter-p12(p11.2) loss (16425296)
• 9p21 loss (17696194)
• 9q34 loss (17696194)
• 22q13.1-q13.31 loss (16425296)

 chromosomal gains

• 1q gain (17696194)
• 3q26.2-q29 gain (16425296)
• 6p22.3 gain (16425296)
• 7p15.2-p14.3 gain (16425296)
• 8p12, 8p21.3 gain (16425296)
• 8p23.2 gain (16425296)
• 8q24.13-q24.21 gain (17696194, 16425296)
• 9q34 gain (17696194, 16425296)
• 16p gain (17696194)
• 19p13.2-p12 gain (16425296)
• 22q11 gain (17696194)
• 22q13.1-q13.32 gain (16425296)

Links

 AGCOH - Atlas of Genetics and Cytogenetics in Oncology and Haematology

Reviews

 Melo JV, Barnes DJ. Chronic myeloid leukaemia as a model of disease evolution in human cancer. Nat Rev Cancer. 2007 Jun;7(6):441-53. PMID: 17522713

 Goldman JM, Melo JV. Chronic myeloid leukemia—advances in biology and new approaches to treatment. N Engl J Med. 2003 Oct 9;349(15):1451-64. PMID: 14534339

References

 MLPA is a powerful tool for detecting lymphoblastic transformation in chronic myeloid leukemia and revealing the clonal origin of relapse in pediatric acute lymphoblastic leukemia. Alpár D, de Jong D, Savola S, Yigittop H, Kajtár B, Kereskai L, Pajor L, Szuhai K. Cancer Genet. 2012 Sep;205(9):465-9. PMID: 22939399

 Brazma D, Grace C, Howard J, Melo JV, Holyoke T, Apperley JF, Nacheva EP. Genomic profile of chronic myelogenous leukemia: Imbalances associated with disease progression. Genes Chromosomes Cancer. 2007 Aug 15; PMID: 17696194

 Hosoya N, Sanada M, Nannya Y, Nakazaki K, Wang L, Hangaishi A, Kurokawa M, Chiba S, Ogawa S. Genomewide screening of DNA copy number changes in chronic myelogenous leukemia with the use of high-resolution array-based comparative genomic hybridization. Genes Chromosomes Cancer. 2006 May;45(5):482-94. PMID: 16425296

History

 Groffen J, Stephenson JR, Heisterkamp N, de Klein A, Bartram CR, Grosveld G. Philadelphia chromosomal breakpoints are clustered within a limited region, bcr, on chromosome 22. Cell 1984;36:93-99. PMID: 6319012

 Heisterkamp N, Stephenson JR, Groffen J, et al. Localization of the c-ab1 oncogene adjacent to a translocation break point in chronic myelocytic leukaemia. Nature 1983;306:239-242. PMID: 6316147

 de Klein A, van Kessel AG, Grosveld G, et al. A cellular oncogene is translocated to the Philadelphia chromosome in chronic myelocytic leukaemia. Nature 1982;300:765-767. PMID: 6960256

 Rowley JD. A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 1973;243:290-293. PMID: 4126434

 Nowell PC, Hungerford DA. Chromosome studies on normal and leukemic human leukocytes. J Natl Cancer Inst 1960;25:85-109. PMID: 14427847