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Acute Myeloid Leukemia (AML) is a life-threatening disease whose induction treatment consists of combination chemotherapy with Idarubicin and Cytarabine for fit patients. Treatment failures are frequent, urging the need for novel treatments for this disease. The DNA Damage Response Mechanism (DDR) comprises numerous molecules and pathways intended to arrest the cell cycle until DNA damage is repaired or else drive the cell to apoptosis. AML-derived cell lines after treatment with Idarubicin and Cytarabine were used for studying the expression profile of 84 DDR genes, through PCR arrays. Utilizing de novo AML patient and control samples we studied the expression of PPP1R15A, CDKN1A, GADD45A, GADD45G, and EXO1. Next, we performed PPP1R15A silencing in AML cell lines in two separate experiments using siRNA and CRISPR-cas9, respectively. Our findings highlight that DDR regulators demonstrate increased expression in patients with high cytogenetic risk possibly reflecting increased genotoxic stress. Especially, PPP1R15A is mainly involved in the recovery of the cells from stress and it was the only DDR gene upregulated in AML patients. The PPP1R15A silencing resulted in decreased viability of Idarubicin and Cytarabine-treated cell lines, in contrast to untreated cells. These findings shed light on new strategies to enhance chemotherapy efficacy and demonstrate that PPP1R15A is an important DDR regulator in AML and its downregulation might be a safe and effective way to increase sensitivity to chemotherapy in this disease. [ABSTRACT FROM AUTHOR]

For patients with intermediate-2 or high risk [according to the International Prognostic Scoring System (IPSS)] myelodysplastic syndromes (MDS), azacitidine treatment offers hematologic improvement (HI) but also has the potential to modify the natural disease course. 'RETRO-AZA-MDS-001', a retrospective chart review study was conducted from February to November 2012 across 17 hematology hospital sites of Greece, aiming to evaluate the clinical efficacy and safety profile of azacitidine in IPSS intermediate-2/high risk adult MDS patients in routine care. A total of 88 patients (median age 74.7 years), with a 6.6 month median (range 1.0-49.5) azacitidine treatment duration were enrolled. The overall response rate [complete response (CR), marrow CR and partial response] was 37.7% (23/61), while stable disease with HI was achieved by 21.3% (13/61). The HI rate was 33.0 % (29/88) and the AML transformation rate 6.8% (6/88). Of the transfusion-dependent patients, 7.3% (3/41) became transfusion-independent during azacitidine treatment. The incidence of non-serious and serious adverse events related to azacitidine was 50.0 and 42.0%, respectively. Patients not receiving prior ESA therapy were expected to be 7.6 times more likely to achieve a clinical response (p = 0.012). The study corroborates the favorable risk-benefit profile of azacitidine for intermediate-2/high risk MDS patients in routine clinical practice. [ABSTRACT FROM AUTHOR]

Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal neoplasms affecting the gastrointestinal tract. Activating mutations in either the KIT or PDGFRa gene are the principal oncogenic triggers with the former accounting for more than 80 % of cases. In the small subset of GIST that are wild type for both the aforementioned changes, other germline or somatic mutations have been identified. GIST exhibit a highly variable clinical behavior and the main prognostic determinants are tumor size, mitotic rate, and location. It is, however, strongly believed that, beyond classic genetics, additional epigenetic phenomena such as DNA hypomethylation and hypermethylation, microRNA alterations, and chromatin modifications underlie GIST tumorigenesis and influence the clinical course and response to standard treatment. This review aims to illuminate current advances in terms of epigenetics in GIST, as well as possible implications in prognosis and therapeutics. [ABSTRACT FROM AUTHOR]

Certain constitutional translocations have been described to be associated with an increased risk of malignant diseases. We report here two patients, one with acute myeloid leukemia (AML) and another with biphenotypic acute leukemia, in whom constitutional translocations t(3;5)(p25;q22) and t(1;14)(p31;q21) were observed, respectively. To our knowledge, none of the above translocations has been previously reported. [ABSTRACT FROM AUTHOR]

Chromosomal abnormalities are of significance in the study of hematologic malignancies. We describe one case of myelodysplastic syndrome (MDS) diagnosed 22 years ago as polycythemia vera (PV) as well as a case of unclassified myeloproliferative disease (MPD) with a poor clinical course. Both patients presented del(11)(q13) as the sole clonal abnormality. This abnormality was also found in two additional cases of MDS. Summarizing the literature, only ten other cases of myeloid malignancies with deletion of 11q involving band q13 as the sole anomaly have been reported. All but one of these cases presented interstitial deletions. [ABSTRACT FROM AUTHOR]