Clinical significance of Gata‐1, Gata‐2, EKLF, and c‐MPL expression in acute myeloid leukemia

Abstract

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...

GATA factors in human neuroblastoma: distinctive expression patterns in clinical subtypes

“…In an attempt to select genes for prognosis prediction in neuroblastoma, among other genes GATA-2 has been observed to be associated with favourable prognosis (Ohira et al, 2005), which is strengthened by our detailed analysis. In patients with acute myeloid leukaemia, GATA-2 was rather associated with poor prognosis (Ohyashiki et al, 1996), although this correlation is challenged by a recent report (Ayala et al, 2009). In breast cancer, high GATA-3 expression correlates with low tumour grade and slow proliferation rates (Usary et al, 2004;Mehra et al, 2005), corresponding to our results.…”

“…They have been suggested both as tumour suppressors and oncogenes (Ohyashiki et al, 1996;Laitinen et al, 2000;Akiyama et al, 2003;Usary et al, 2004;Engelsen et al, 2008;Ayala et al, 2009;Thurisch et al, 2009). Thus, repression or activation of GATA function could be important for cancer biology, and the precise function may depend on cofactors and the specific cellular context.…”

Overexpression of GATA2 predicts an adverse prognosis for patients with acute myeloid leukemia and it is associated with distinct molecular abnormalities

“…1 More recently, whole-genome and whole-exome sequencing technologies have been used to further unravel the genomic landscape of AML-NK. Novel mutations so far identified in AML-NK using these approaches include those involving the IDH1, IDH2 and DNMT3A genes, [4][5][6] and others are expected to be found in the future by sequencing additional AML-NK genomes.…”

“…Strong GATA2 expression was found in 87% of AML patients (54/62) using single-round RT-PCR. 4 More recently, Ayala et al 5 analyzed the expression of GATA2 in 41 patients with AML by real-time quantitative RT-PCR (QRT-PCR). They found that 21 cases had expression of GATA2 (52%), and defined overexpression as the expression values that were over the median value in GATA2-expressing patients.…”

“…However, the small sample size used in this study highlights the need for further studies. 5 Using a Cox proportional hazards model, we next assessed the influence of distinct baseline variables on OS, DFS and EFS: age, sex, bone marrow blasts at diagnosis, white blood count at diagnosis, AML type, FLT3-ITD and NPM1 mutations, and GATA2 expression groups (Supplementary Table 3). Notably, multivariate analyses demonstrated that GATA2 overexpression CEBPA mutation analyses were performed in normal karyotype cases lacking FLT3-ITD and NPM1 mutations.…”