Search results for "Promyelocytic"

Characteristics and outcome of adult patients with acute promyelocytic leukemia and increased body mass index treated with the PETHEMA Protocols

2020

PETHEMA, HOVON, PALG, GATLA cooperative groups.

Tamibarotene in patients with acute promyelocytic leukaemia relapsing after treatment with all-trans retinoic acid and arsenic trioxide

2015

Treatment of acute promyelocytic leukaemia (APL) with arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) is highly effective first-line therapy, although approximately 5-10% of patients relapse. Tamibarotene is a synthetic retinoid with activity in APL patients who relapse after chemotherapy and ATRA, but has not been studied in relapse after treatment with ATO and ATRA. We report on a phase II study of tamibarotene in adult patients with relapsed or refractory APL after treatment with ATRA and ATO (n = 14). Participants were treated with tamibarotene (6 mg/m(2) /d) during induction and for up to six cycles of consolidation. The overall response rate was 64% (n = 9), the rate of comp…

Deficiency of the promyelocytic leukemia protein fosters hepatitis C-associated hepatocarcinogenesis in mice.

2012

Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of hepatocellular carcinoma (HCC). We have recently shown that HCV core protein mediates functional inactivation of the promyelocytic leukemia (PML) tumor suppressor pathway. However, the role of PML in HCC development yet remains unclear. To clarify the function of PML in liver carcinogenesis and HCV-associated pathogenesis we crossed PML-deficient mice with HCV transgene (HCV-Tg) expressing mice and treated the resulting animals with DEN/Phenobarbital, an established protocol for liver carcinogenesis. Seven months after treatment, livers …

Factors Determining Sensitivity and Resistance of Tumor Cells to Arsenic Trioxide

2012

Previously, arsenic trioxide showed impressive regression rates of acute promyelocytic leukemia. Here, we investigated molecular determinants of sensitivity and resistance of cell lines of different tumor types towards arsenic trioxide. Arsenic trioxide was the most cytotoxic compound among 8 arsenicals investigated in the NCI cell line panel. We correlated transcriptome-wide microarray-based mRNA expression to the IC(50) values for arsenic trioxide by bioinformatic approaches (COMPARE and hierarchical cluster analyses, Ingenuity signaling pathway analysis). Among the identified pathways were signaling routes for p53, integrin-linked kinase, and actin cytoskeleton. Genes from these pathways…

Conventional induction and post-remission therapy in APL: have we arrived?

2014

Since the introduction of all-trans-retinoic acid, the use of this molecularly targeted treatment in combination with anthracycline-based chemotherapy has completely changed the prognosis of acute promyelocytic leukemia (APL) turning it into the most curable acute myeloid leukemia. Also, the use of risk-adapted protocols has optimized the drug combination and the most appropriate dose intensity for each subset of patients classified according to both risk of relapse and vulnerability to drug toxicity. Recent developments have included the investigation of the role of arsenic trioxide (ATO) as front-line treatment after its success in relapsed APL, both to minimize or even omit the use of cy…

Prognostic Impact of Mutant to Wild-Type Ratio and Insertion Site in Acute Myeloid Leukemia with FLT3 Internal Tandem Duplication

2012

Abstract Abstract 785 Background: FLT3 internal tandem duplications (FLT3-ITD) occur in about 25% of acute myeloid leukemia (AML), are associated with cooperating gene mutations (NPM1, DNMT3A), and confer an adverse prognosis. Several studies have indicated that the unfavorable impact of FLT3-ITD is influenced by a number of factors, such as the mutant to wild-type ratio (allelic ratio), insertion site of FLT3-ITD in the beta1 sheet of the tyrosine kinase domain 1, and the molecular background of cooperating mutations. Aims: To evaluate the relative impact of FLT3-ITD allelic ratio and insertion site, as well as cooperating genetic lesions on prognosis and treatment decision making in a lar…

The experience of the International Consortium on Acute Promyelocytic Leukemia in monitoring minimal residual disease in acute promyelocytic leukaemia

2016

Metformintreatment Overcomes ATRA-Resistance in Acute Promyelocytic Leukemia and Increases FOXO3A Expression

2018

Abstract Introduction: FOXO3A is a transcription factor shown to be involved in all-trans retinoic acid (ATRA)-induced granulocytic differentiation and apoptosis in acute promyelocytic leukemia (APL). Its biological activity may be significantly enhanced upon metformin, raising the possibility that ATRA and Metformin may act synergistically; which could be useful to overcome ATRA resistance. Despite progress in APL treatment, approximately 10-15% of patients will relapse after treatment with ATRA and anthracyclines and frequently present with ATRA resistance. Relapsed patients respond well to arsenic trioxide (ATO) treatment, but the cost of ATO is a significant barrier in many countries. A…

Special Situations in APL

2017

The introduction of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) as the mainstay therapy of acute promyelocytic leukemia (APL) has drastically changed the outcome of this hematologic malignancy into one of the first to receive a targeted treatment. Using frontline treatment strategies including these agents in combination with standard cytotoxic drugs has provided outstanding therapeutic results in most patients. In spite of the achievement of brilliant results in the majority of patients, some special situations still require the implementation of changes from the conventional therapeutic approach. In this chapter, we will review and discuss the management of APL in older and …

PML as a potential predictive factor of oxaliplatin/fluoropyrimidine-based first line chemotherapy efficacy in colorectal cancer patients

2012

PML regulates a wide range of pathways involved in tumorigenesis, such as apoptosis, which is also one of the main mechanisms through which oxaliplatin and fluoropyrimidine exert their antineoplastic activity. The present study aims to investigate PML expression as a predictive factor of oxaliplatin/fluoropyrimidine therapy efficacy. Seventy-four metastatic colorectal cancer patients who received oxaliplatin/floropyrimidine-based first line therapy have been included in this retrospective study. PML expression was assessed by immunohistochemistry. PML down-regulation was detected in 39 (52.7%) patients (14 complete and 25 partial PML loss). RR was significantly lower (25.6%) in patients wit…