In fact, hypermethylation of genes involved in the TP53 pathway is an independent poor prognostic factor in patients with ALL. By Dong-qing Wang, Hai-tao Zhu, Yan-fang Liu, Rui-gen Yin, Liang Zhao, Zhi-jian Zhang, Zhao-liang Su, Yan-Zhu, Hui-qun Lu, Juan Hong and Jie Zhang, By Fernando Abollo-Jimenez, Elena Campos-Sanchez, Ana Sagrera, Maria Eugenia Muñoz, Ana Isabel Galan, Rafael Jimenez and Cesar Cobaleda. BCL-2 inhibits apoptosis by inactivating BAX and BAK.5 Increased expression of pro-survival BCL-2 relative to the pro-apoptotic protein BAX is associated with reduced complete remission rates, earlier relapse, and inferior overall survival in patients receiving intensive chemotherapy for AML. (Hishidaet al, 2003) This increased expression may, in turn, increase the conversion of dUMP to dTMP, thereby; decreasing uracil levels and the consequent erroneous incorporation of uracil into DNA of rapidly dividing hematopoietic stem cells, and could work protectively against the development of ALL. In stratified studies by tumor site, there was a statistically significant reduced risk with ALL. Treatment of relapsed or refractory acute lymphoblastic leukemia in adults. Del Poeta D, Venditti A, Del Principe MI, et al. (Lordelo et al, 2011) Association studies have been described between C677T and A1298C MTHFR polymorphisms and risk of leukemia (Skibola et al, 1999; Franco et al., 2001; Robien and Ulrich, 2003; Gallegos et al, 2008), which produces an decreased catalytic activity of MTHFR and subsequent availability of 5,10-MeTHF and SAM, have been extensively studied in relation to childhood leukemia, these findings have been inconsistent and their frequency vary among ethnic groups.

The presence of the triple repeat leads to increased levels of gene expression and a reduction in DNA damage. (Marchesi et al, 2011), MLL gene encodes a 500 kD protein containing several conserved functional domains, a target of proteolytic activity of Caspasa 1, a cleaving protein specialized in N-terminal fragments of 320 kD and C-terminal of 180 kD. The AML-PT represent 10 to 15% of total AML and its incidence is increasing substantially in recent years, (Ng et al, 2000) the AML-PT are often associated with clonal cytogenetic abnormalities similar to those found in newly diagnosed AML, but with higher incidence of poor prognosis karyotypes and have particular clinical and biological features that include a poor response to CT commonly used in the treatment of AML and therefore have a significantly adverse prognosis. The molecular alterations that are required for the development of a malignant disease is a rare phenomenon when one considers the large number of target cells susceptible to this condition, in other words, a single genetic change rarely be sufficient for developing a malignant tumor.

This content does not have an Arabic version. Although the number of mutations per AML genome or exome is lower than for most other cancers,8 with an average of only five recurrent mutations per AML genome, at least one driver mutation can be identified in 96% of patients with de novo AML, and 86% of patients have two or more driver mutations.9 Tremendous diversity exists in the overlap of these mutations and the subclonal genomic architecture of the disease.

(Lan et al, 2004) Other compounds studied with controversial relationship, are some agricultural pesticides, heavy metals, smoke snuff, alcohol intake and exposure to cosmic rays of airlines pilots.

(Pui et al, 2011), This knowledge has increased our understanding of leukemogenesis and prognosis, and additionally has served as foundation for the development of targeted therapy. The treatment response is not significantly different from those of patients with de novo AML. Secondary hematological malignancies are a serious complication of cancer treatment. (figure 4) The 844ins68 polymorphism was associated in Down Syndrome (DS) with leukemia myeloblasts, detecting a 4.6-fold higher rate (P < 0.001) when compared to non-DS individuals. Recent identification of novel genetic alterations and … The clinical behavior is more aggressive, patients have a higher percentage of failure of remission, relapse rate is also higher as well, and the central nervous system infiltration compared with B-cell ALL type.

Where exert their pharmacological action and pharmacodynamics specified; only a small part reaches the tissue-receptor-target enzyme, while most are metabolized and eliminated. Acute lymphoblastic leukemia. In ALL, the majority of the cases, the transformation affects the B lineage cells. We share our knowledge and peer-reveiwed research papers with libraries, scientific and engineering societies, and also work with corporate R&D departments and government entities. Then, the well-documented in utero origin of ALL has led to hypothesize that deficient folate intake may be important in its etiology. (Zornoza et al, 2011). (Pui et al, 2011), The current model involves several steps, the fusion of these genes can occur already during fetal development and is the initial event, but is not sufficient for the neoplastic transformation (Fuka et al, 2011).

Leukemia and other cancers share biological characteristics, as clonality. Many of the altered genes are tumor suppressor that have a recessive character and therefore, requires the loss of both alleles. (Levine and Blomifield, 1992) Although most secondary leukemias are acute AML, there have been reports of lymphoid leukemia and CML is associated with CT. (Andersen et al, 2000; Krishnan et al, 2000; Pedersen-Bjergaard et al, 2002), The AML are hematologic malignancies characterized by the uncontrolled myeloid blast proliferation in the bone marrow and in peripheral tissues. When Notch expression is suppressed, the p53 pathway is activated and leads to tumor regression. Many signs and symptoms of acute lymphocytic leukemia mimic those of the flu. So that although the macrophage plays an important role in the destruction of cancer cells, leukemic cells with greater metabolic potential, and the potential escapes annihilating the macrophage. Pui CH, Schrappe M, Ribeiro RC, Niemeyer CM.  |  In patients with topoisomerase inhibitor exposure, cytogenetic testing reveals frequent 11q23, inversion 16, or t(15;17) translocations.1,3 Overall, patients with therapy-related AML have shorter overall survival and poorer outcomes than de novo AML cases. (Valiket al, 2004; Lightfoot et al, 2005) Although, it has been proposed that arise by genetics and environmental factors. (Gomez et al, 2012), NOTCH target genes are mainly cyclin D1 and c-Myc. BCL-2 inhibition targets oxidative phosphorylation and selectively eradicates quiescent human leukemia stem cells. (Inskip, 1999; Smith et al, 2002) Estimates show, that patients undergoing RT for the treatment of malignancies or other non-malignant diseases has a risk of two to three times more to develop AML-PT/MDS-PT. Transcription factors generally require interacting with other proteins to act, for example: Fos transcription protein dimerizes with the transcription factor Jun to form the AP1 transcription factor is really a complex, and this increases the expression of several genes control cell division, all they have been involved in the development of leukemia. When an oncogen is activated by mutation, encoded protein is structurally modified so that enhances its transforming activity, thus remains on active status, continuously transmitting signals through the binding of tyrosine and treonina cinasa. Polymorphic variants of several genes, diet, environmental exposure to carcinogens and individualities of immune system are potential factors that could be increase predisposition to leukemia. In this sense, recently has been reported that the incidence of chromosomal change is related with the age, so the translocation t(9;22)(q34;q11) increases in each successive decade, up to 24% between the 40-to 49 years old, the t(4;11) (q21;q23) and t(1;19) (q23;q13) are rare in patients older than 60 years old, but t (8;14) (q24;q32) and t(14;18)(q32;q21) increased with age.   •  Notice This chapter is distributed under the terms of the Creative Commons Attribution 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. This break off at a chromosome can turn on oncogenes or turn off tumor suppressor genes leading to cancers. The results of studies of gene expression analysis of high resolution whole genome, copy number alterations of DNA, loss of heterozygosity epigenetic changes and whole genome sequencing, have allowed the recognition of new genetic alterations, so that virtually all patients with ALL can be classified according to the specific genetic abnormality.