The aim of this study was to evaluate the biological correlation and prognostic impact of Gata-1, Gata-2, EKLF, and c-MPL transcript level in a group of 41 acute mieloid leukemia (AML) patients. Gata-1 overexpression was related to advanced age and a low percentage of bone marrow blasts and was associated with the expression of CD34 antigen and lymphoid T markers. The negative impact of Gata-1 expression on the probability of achieving complete remission has been confirmed. Gata-2 overexpression was associated with a low percentage of blasts in BM and males. Expression of c-MPL was associated with CD341 AML and M2 FAB AML subtype. A higher expression of EKLF was found in secondary AML versus primary AML. Nevertheless, patients expressing EKLF had a longer overall survival and event free survival than those patients that did not express EKLF. Our study has identified expression of EKLF as a factor with a favorable impact on prognosis in AML. Am. J. Hematol. 84:79-86, 2009. V V C 2008 Wiley-Liss, Inc.
IntroductionBlood cells are derived from a small number of pluripotent hematopoietic stem cells (HSCs) endowed with the capacity for self-renewal [1]. Specific hematopoietic transcription factors are crucial for self renewal, choice of cell fate, and cell differentiation during normal hematopoiesis [2]. Acute myeloid leukemia (AML) is characterized by the uncontrolled proliferation of myeloid cells that accumulate at various stages of development, where their further differentiation appears to be blocked. Although disturbance of the expression of transcription factors regulating proliferation, survival, and differentiation of myeloid progenitors is almost certainly a requisite for the pathogenesis of AML, a direct link to myeloid leukemogenesis has been formally demonstrated in only a few transcription factors [2].In AML, disruptions of transcription factors themselves seem to be able to enhance and/or block proliferation of the leukemic cells [2-4] because of either the effect on the factors of fusion proteins generated by chromosomal translocations or mutations in the transcription factors.However, even in the absence of the alterations previously mentioned, deregulation of hematopoietic transcription factors is to be expected in AML cells. Recent studies have provided evidence that differential expression of a limited number of genes, that include certain transcription factors, can be useful to classify AML and are related to variations in patient survival [5][6][7][8].Relevant changes in megakaryocytic and erythroide linage are a feature of M6 and M7 AML, but changes in transcription factors involved in erythroid and megakaryocyte differentiation can also be expected in other AML subtypes. The expression of the transcription factors involved in differentiation of the common bipotent progenitor [9] could affect the clinical course and response to treatment of all types of AML.With the purpose of bringing forward information in the deregulation of normal hematopoetic factors in AML, expression of several transcript...