Future perspectives

It is clear that leukemia in DS follows an independent genetic trajectory compared to leukemia in non-DS patients. Identifying and confirming the altered genetic pathway will improve diagnosis and enhance treatment strategies. Large-scale population studies are required for establishing appropriate treatment strategies and thus preventing undue toxicities in patients.

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1. Xavier A.C., Ge Y., Taub J.W. Down Syndrome and Malignancies: A Unique ClinicalRelationship. J Mol Diagn. 2009;11(5):371–80.

2. Rabin K.R., Whitlock J.A. Malignancy in Children with Trisomy 21. Oncologist. 2009;14(2):164–73.

3. Forestier E., Izraeli S., Beverloo B., et al. Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study. Blood. 2008;111:1575–83.

4. Hertzberg L., Vendramini E., Ganmore I., et al. Down syndrome acute lymphoblastic leukemia, a highly heterogenous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood. 2010;115:1006–17.

5. Mullighan C.G., Collins-Underwood J.R., Phillips L.A.A., et al. Rearrangement of CRLF2 in B-progenitor and Down syndrome associated acute lymphoblastic leukemia. Nat Genet. 2009;41(11):1243–46.

6. Malinge S., Izraeli S., Crispino J.D. Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome. Blood. 2009;113:2619–28.

7. Kanegane H., Watanabe S., Nomura K., Xu G., Ito E., Miyawaki T. Distinct clones are associated with the development of transient myeloproliferative disorder and acute megakaryocytic leukemia in a patient with Down syndrome. Int J Hematol. 2007;86(3):250–2.

8. Key player found for a cancer typical in Down syndrome [news release]. Children’s Hospital Boston; March 1, 2010. http://www.eurekalert.org/pub_releases/2010-03/chb-kpf030110.php. Accessed May 20, 2012.

9. Maloney K.W., Carroll W.L., Carroll A.J., et al. Down syndrome childhood acute lymphoblastic leukemia has a unique spectrum of sentinel cytogenetic lesions that influences treatment outcome: a report from the Children’s Oncology Group. Blood. 2010;116:1045–50.

10. Loudin M..G, Wang J., Leung H.C.E., et al. Genomic profiling in Down syndrome acute lymphoblastic leukemia identifies histone gene deletions associated with altered methylation profiles. Leukemia. 2011;25:1555–63.

11. Yokoyama T., Toki T., Aoki Y., et al. Identification of TRIB1 R107L gain-of-function mutation in human acute megakaryocytic leukemia. Blood. 2012;119:2608–11.

12. Blink M., van den Heuvel-Eibrink M.M., de Haas V., et al. Low frequency of type-I and type-II aberrations in myeloid leukemia of Down syndrome, underscoring the unique entity of this disease. Haematologica. 2012;97(4):632–4.

13. New chromosomal abnormality identified in leukemia associated with Down syndrome [news release]. St. Jude Children’s Research Hospital; October 18, 2009. http://www.eurekalert.org/pub_releases/2009-10/sjcr-nca101509.php. Accessed May 20, 2012.

14. Ensor H.M., Schwab C., Russell L.J., et al. Demographic, clinical, and outcome features of children with acute lymphoblastic leukemia and CRLF2 deregulation: results from the MRC ALL97 clinical trial. Blood. 2011;117:2129–36.

15. Lundin C., Hjorth L., Behrendtz M., et al. High Frequency of BTG1 Deletions in Acute Lymphoblastic Leukemia in Children with Down Syndrome. Genes Chromosomes Cancer. 2012;51:196–206.

16. Sorrell A.D., Alonzo T.A., Hilden J.M., et al. Favorable survival maintained in children who have myeloid leukemia associated with down syndrome using reduced-dose chemotherapy on children’s oncology group trial A2971. Cancer. 2012;doi: 10.1002/cncr.27484.

17. Moritake H., Yamada A., Kimoto Y., et al. Acute megakaryoblastic leukemia and severe pulmonary fibrosis in a child with Down syndrome: Successful treatment with ultra low-dose cytarabine using GATA1 mutation to monitor minimal residual disease. Am J Hematol. 2012;87(4)447–50.

18. Rabin K.R., Smith J., Kozinetz C. Myelosuppression and Infectious Complications in Children With Down Syndrome and Acute Lymphoblastic Leukemia. Pediatric Blood Cancer. 2012;58:633–35.

19. Reinhardt D., Reinhardt K., Neuhoff C., et al. GATA1-mutation associated leukemia in children with trisomy 21 mosaic. Klin Padiatr. 2012;224(3):153–5.