Trisomy Disorders

Trisomy 5

Clinics and Pathology

Disease

Trisomy 5 is found in both acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML), but very rarely as the sole karyotypic abnormality.

Clinics

In childhood ALL, an extra chromosome 5 is commonly encountered in cases with hyperdiploidy > 50 chromosomes. The presence of trisomy 5 in high hyperdiploid childhood ALL is associated with a less favourable clinical outcome. Trisomy 5 as a sole abnormality in ALL is exceedingly rare and described in only 3 cases, including 2 adult ALL and 1 paediatrics case occurring in a 12-year old girl. Trisomy 5 has been described in 19 cases of AML. Gain of chromosome 5 usually occurs in association with other cytogenetics aberrations, although very rarely it may exist as the sole abnormality. A case of AML-M2 with normal karyotype at diagnosis showed trisomy 5 as the sole abnormality at relapse, and a case of AML-M5 showed trisomy 5 as the only chromosome aberration in 3% of 59 metaphases at presentation. A further case of AML-M4 showed a clone with trisomy 5 as the sole abnormality together with a second clone with trisomy 5 and evolutionary change. In the other 16 cases, trisomy 5 was found in association with numerical (n = 4), structural changes (n = 4), or both numerical and structural changes (n = 8).

A number of interesting observations with respect to AML and trisomy 5 should be noted. First, an association between trisomy 5 and t(8;21) (n = 3) and trisomy 8 (n = 6) is observed. Second, five out of 6 cases with concurrent trisomies 5 and 8 show monocytic differentiation and are diagnosed as either AML-M4 or M5. Finally, trisomy 5 has been described in all FAB subtypes of AML except acute promyelocytic leukaemia.Given the rarity of trisomy 5 in AML, it is possible that the associated cytogenetic aberrations such as t(8;21) or trisomy 8 and not trisomy 5 per se that predicts for the myeloid phenotype.

Prognosis

Trisomy 5 in childhood ALL with hyperdiploidy > 50 chromosomes is associated with a poorer clinical outcome. Among the 3 cases of ALL with trisomy 5 as the sole karyotypic abnormality, 2 (one case each of adult and paediatric ALL) showed short survival whilst one adult ALL case showed event free survival of 4 years off chemotherapy.

Among 19 AML patients with trisomy 5, complete remission was achieved in 8 and the median overall survival was 15 months. For the remaining 11 patients, 2 achieved partial remission and died, 4 did not attain remission at all, 1 was not treated, and the status of 4 patients was unknown.

Infobiogen

Bibliography

Multiple leukemic clones in acute leukemia of childhood. Morse HG, Ducore JM, Hays T, Peakman D, Robinson A. Hum Genet 1978; 40: 269-278. Medline 273006   Evolution of karyotypes in acute nonlymphocytic leukemia. Testa JR, Mintz U, Rowley JD, Vardiman JW, Golomb HM. Cancer Res 1979; 39: 3619-3627. Medline 476688   Nonrandom cytogenetic changes in New Zealand patients with acute myeloid leukemia. Fitzgerald PH, Morris CM, Fraser GJ, Giles LM, Hamer JW, Heaton DC, Beard ME. Cancer Genet Cytogenet 1983; 8: 51-66. Medline 6572548   High-resolution chromosomes as an independent prognostic indicator in adult acute nonlymphocytic leukemia. Yunis JJ, Brunning RD, Howe RB, Lobell M. N Engl J Med 1984; 311: 812-818. Medline 6472383   Chromosomal alterations in acute leukemia patients studied with improved culture methods. Testa JR, Misawa S, Oguma N, Van Sloten K, Wiernik PH. Cancer Res 1985; 45: 430-434. Medline 3855285   Myeloblastoma with an 8;21 chromosome translocation in acute myeloblastic leukemia. Abe R, Umezu H, Uchida T, Kariyone S, Maseki N, Kaneko Y,Sakurai M. Cancer 1986; 58: 1260-1264. Medline 3461872   Acute myelogenous leukemia with translocation t(8;21): a cytogenetic study of seven cases. Sessarego M, Mareni C, Panarello C, Garre L, Frassoni F, Boccaccio P, Ajmar F. Cancer Genet Cytogenet 1986; 20: 363-368. Medline 3455871   Cytogenetics and acute non lymphocytic leukemia. Palka G, Fioritoni G, Geraci L, Calabrese G, Mosca L, Peca S, Guanciali Franchi P, Spadano A, Arduini A, Torlontano G. Ann Genet 1987; 30: 39-46. Medline 3498428   Detection of karyotypic abnormalities in most patients with acute nonlymphocytic leukemia by adding ethidium bromide to short-term cultures. Misawa S, Yashige H, Horiike S, Taniwaki M, Nishigaki H, Okuda T, Yokota S, Tsuda S, Edagawa J, Imanishi H. Leuk Res 1988; 12: 719-729. Medline 3193811   Specific chromosome changes and nonoccupational exposure to potentially carcinogenic agents in acute leukemia in China. Li YS, Zhao YL, Jiang QP, Yang CL. Leuk Res 1989; 13: 367-376. Medline 2747268   Cytogenetic study of a case of childhood erythroleukemia. Duarte MH, Tone LG, Soares LR, dos Santos SA. Cancer Genet Cytogenet 1990;49:25-30. Medline 2397470   Clinical and cytogenetic correlations of abnormal megakaryocytopoiesis in patients with acute leukemia and chronic myelogenous leukemia in blast crisis. Lee EJ, Schiffer CA, Tomiyasu T, Testa JR. Leukemia 1990; 4: 350-353. Medline 2388480   Unusual translocations and other changes in acute leukemia. Ferro MT, del Potro E, Krsnik I, Villegas A, Fernandez-Ranada JM, Resino M, Garcia-Sagredo JM, San-Roman C. Cancer Genet Cytogenet 1991; 54: 163-171. Medline 1884348   Abnormalities of chromosome 16q in myeloid malignancy: 14 new cases and a review of the literature. Betts DR, Rohatiner AZ, Evans ML, Rassam SM, Lister TA, Gibbons B. Leukemia 1992; 6: 1250-1256. Medline 1453770   A case of trisomy 5 in a Philadelphia positive leukemia. Smadja N, Varette C, Louvet C, Gramont A, Krulik M. Cancer Genet Cytogenet 1992 ;61: 216-217. Medline 1638509   A new case of trisomy 5 as sole cytogenetic anomaly in acute myeloid leukemia. Rios R, Sole F, Montes C, Vicente A, Perez MM, Valle M, Gascon F. Cancer Genet Cytogenet 1995; 84: 120-122. Medline 8536225   Trisomy 5 in two cases of acute monocytic leukemia with hyperdiploid clones. Ma SK, Wan TS, Au WY, Chan LC. Leuk Res 1998; 22: 961-964. Medline 9766757   Prognostic impact of trisomies of chromosomes 10, 17, and 5 among children with acute lymphoblastic leukemia and high hyperdiploidy (> 50 chromosomes). Heerema NA, Sather HN, Sensel MG, Zhang T, Hutchinson RJ, Nachman JB, Lange BJ, Steinherz PG, Bostrom BC, Reaman GH, Gaynon PS, Uckun FM. J Clin Oncol 2000; 18: 1876-1887. Medline 10784628   Trisomy 5 as a sole cytogenetic abnormality in pediatric acute lymphoblastic leukemia. Sandoval C, Mayer SP, Ozkaynak MF, Tugal O, Jayabose S. Cancer Genet Cytogenet 2000; 118: 69-71. Medline 10731595