Print version ISSN 1516-8484
Rev. Bras. Hematol. Hemoter. vol.33 no.6 São Paulo Dec. 2011
Jesús M Hernández-Rivas
Centro de Investigación del Cáncer - IBMCC, Universidad de Salamanca, Consejo Superior de Investigaciones Científicas - CSIC and Hematology Service, Hospital Universitario de Salamanca, Spain
Secondary myeloid neoplasias are a heterogeneous group of diseases characterized by the proliferation of myeloid cells; they were recently recognized by the World Health Organization (WHO) as an entity. The wide use of chemotherapy and better diagnosis of hematological malignancies has caused a growth in the number of secondary malignancies. Most of them are myeloid: a) myelodysplastic syndromes (MDS), a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and dysplastic changes in bone marrow and peripheral blood with the risk of transformation to acute myeloid leukemia (AML) or b) sometimes the previous disease directly evolves to an overt AML. Usually the prognosis of patients with a secondary myeloid neoplasia is poor, especially when the previous disease is a MDS. However, patients may achieve a complete response. In this situation, progenitor stem cell transplantation is the best therapy.
Cytogenetic analysis still plays a pivotal role in the diagnosis of hematological diseases. Cytogenetics and mutational analysis are the main prognostic tools in both AML and MDS. For this reason, cytogenetic studies are critical in the correct management of these diseases. There are several cytogenetic abnormalities associated with better prognosis, such as translocations involving core binding factors in AML patients, and losses in 20q, 5q or chromosome Y in MDS. In contrast, many others abnormalities are associated with dismal prognoses, such as the presence of a complex karyotype, abnormalities of either chromosome 3 or chromosome 7 and, in case of AML, the loss of the long arm of chromosome 5.
All of these abnormalities are included in the new staging system for MDS (IPSS-2). Recently new data regarding the presence of abnormalities in chromosome 7 in primary MDS showed that the presence of a partial deletion of the long arm of this chromosome (7q-) is associated with a better prognosis than monosomy 7.(1) This abnormality is a common event in secondary MDS and AML and the potential value of this observation in secondary MDS should be addressed. In this issue of the Revista Brasileira de Hematologia e Hemoterapia a new observation highlighted the importance of performing cytogenetic studies in secondary MDS.(2)
Over recent years, the wide use of microarrays and, more recently, the possibility of sequencing the human genome have provided new insights into knowledge of the molecular mechanisms involved in MDS and AML. Analysis of the gene expression profile by means of microarray technology demonstrated the presence of new pathways involved in the pathogenesis of these disorders, although studies focusing on secondary myeloid diseases are lacking.(3) Since the sequencing of the entire genome of the first hematological malignancy, a patient with AML,(4) several papers have shown the interest of the detection of new genes involved in these diseases.(5) Some of these papers have also described the involvement of new functions involved in myeloid diseases such as the spliceosome mechanism that could play an essential role in the genesis of both MDS and AML.(6) Therefore, near future investigations should provide more information of the genes involved in secondary myeloid diseases. The challenges will be to understand these genes which are thought to be drivers in the genesis of secondary myeloid neoplasias and, more importantly, to identify new therapeutic targets.
1. Cordoba I, González-Porras JR, Nomdedeu B, Luño E, de Paz R, Such E, et al. Better prognosis for patients with del(7q) than for patients with monosomy 7 in myelodysplastic syndrome. Cancer 2011 Jun 29. doi: 10.1002/cncr.26279. [Epub ahead of print] [ Links ].
2. Tanizawa RS, Azevedo Neto RS, Kumeda K, Leal AM, Ferreira PB, Velloso ED. Karyotypic and fluorescent in-situ hybridization study of the centromere of chromosome 7 in secondary myeloid neoplasms. Rev Bras Hematol Hemoter. 2011;33(6):425-31. [ Links ]
3. Theilgaard-Mönch K, Boultwood J, Ferrari S, Giannopoulos K, Hernandez-Rivas JM, Kohlmann A, et al. Gene expression profiling in MDS and AML: potential and future avenues. Leukemia. 2011;25(6):909-20. [ Links ]
4. Mardis ER, Ding L, Dooling DJ, Larson DE, McLellan MD, Chen K, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med. 2009;361(11):1058-66. [ Links ]
5. Taskesen E, Bullinger L, Corbacioglu A, Sanders MA, Erpelinck CA, Wouters BJ, et al. Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity. Blood. 2011;117(8):2469-75. [ Links ]
6. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478(7367):64-9. [ Links ]
Jesús Maria Hernández Rivas
Servicio de Hematología
Pso. San Vicente 58-182
37007 - Salamanca, Spain
Phone: + 34-923-291384 Fax: + 34-923-294624
Conflict-of-interest disclosure: The author declares no competing financial interest