Using the longest run subsequence problem within homology-based scaffolding.

Genome assembly is one of the most important problems in computational genomics. Here, we suggest addressing an issue that arises in homology-based scaffolding, that is, when linking and ordering contigs to obtain larger pseudo-chromosomes by means of a second incomplete assembly of a related species. The idea is to use alignments of binned regions in one contig to find the most homologous contig in the other assembly.

Efficacy of azacitidine is independent of molecular and clinical characteristics - an analysis of 128 patients with myelodysplastic syndromes or acute myeloid leukemia and a review of the literature.

Azacitidine is the first drug to demonstrate a survival benefit for patients with MDS. However, only half of patients respond and almost all patients eventually relapse. Limited and conflicting data are available on predictive factors influencing response.

Early aberrant DNA methylation events in a mouse model of acute myeloid leukemia.

Background: Aberrant DNA methylation is frequently found in human malignancies including acute myeloid leukemia (AML). While most studies focus on later disease stages, the onset of aberrant DNA methylation events and their dynamics during leukemic progression are largely unknown.

Methods: We screened genome-wide for aberrant CpG island methylation in three disease stages of a murine AML model that is driven by hypomorphic expression of the hematopoietic transcription factor PU.

Impaired mitochondrial gene transcription in myelodysplastic syndromes and acute myeloid leukemia with myelodysplasia-related changes.

Objective: To examine mitochondrial gene expression in hematopoietic progenitor cells of patients with myelodysplastic syndromes (MDS). Mitochondrial pathology in MDS is suggested by abnormal mitochondrial iron accumulation, increased apoptosis, and a high frequency of acquired mitochondrial DNA mutations in bone marrow cells.

Materials And Methods: Mitochondrial gene expression was measured by real-time reverse transcription polymerase chain reaction in CD34(+) bone marrow cells from 37 patients with MDS (22 refractory cytopenia with multilineage dysplasia, 9 refractory anemia with excess of blasts [5-9% marrow blasts], 6 refractory anemia with excess of blasts [10-19% marrow blasts]), 14 cases of acute myeloid leukemia with myelodysplasia-related changes (acute myeloid leukemia-MDS), and 9 normal controls.

Therapy adapted to molecular response in patients with chronic myelogenous leukaemia in first chronic phase: results of the Duesseldorf study.

This study evaluates response-adapted treatment of chronic myelogenous leukaemia (CML) in chronic phase using molecular response criteria. bcr-abl/G6PDH ratios were assessed by Light-Cycler quantitative real-time polymerase chain reaction (PCR( in 277 peripheral blood samples from 33 patients, before and every 3 months during therapy. Sixty-six per cent (22/33) of the patients fulfiled our molecular response criterion of > or = 1 log decrease in bcr-abl transcript after 6 or > or = 2 log decrease after 9 and every following 3 months.

Analysis of mitochondrial DNA in 104 patients with myelodysplastic syndromes.

Objective: To determine the frequency and spectrum of somatic mutations of mitochondrial DNA (mtDNA) in bone marrow of patients with myelodysplastic syndrome (MDS).

Materials And Methods: Analysis included 104 patients with MDS (24 refractory anemia, 32 refractory anemia with ringed sideroblasts, 34 refractory anemia with excess of blasts, 7 refractory anemia with excess of blasts in transformation to acute leukemia, and 7 chronic myelo-monocytic leukemia), 3 patients with acute myeloid leukemia from MDS, and 36 patients with myeloproliferative disease (23 chronic myeloid leukemia, 9 polycythemia vera, 4 idiopathic myelofibrosis). Mutation scanning was performed using heteroduplex analysis with denaturing high-performance liquid chromatography (dHPLC).

Mitochondrial DNA mutations in differentiated thyroid cancer with respect to the age factor.

Introduction: Increased numbers of mitochondria in differentiated thyroid cancer and, most strikingly, mutations in human mitochondrial DNA (mtDNA) in older people have led to speculation that mtDNA mutations might contribute to aging or accumulate in postmitotic tissues with age. Mutation analyses of mtDNA in papillary (PTCs) and follicular (FTCs) thyroid carcinomas have been limited to date. The significance and frequency of mtDNA mutations in PTC and FTC are therefore controversial, as is age dependence.

Optimized PCR fragments for heteroduplex analysis of the whole human mitochondrial genome with denaturing HPLC.

Denaturing high pressure liquid chromatography (dHPLC) is an efficient method for discovery of unknown mutations by heteroduplex analysis of PCR fragments. For comprehensive mutation scanning of the whole 16.569 bp human mitochondrial genome, we developed a set of 67 primer pairs defining overlapping PCR fragments that are well suited for heteroduplex analysis.

Acquired PTPN11 mutations occur rarely in adult patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.

Myelodysplastic syndromes (MDS) are comprised of a heterogeneous group of stem cell disorders characterized by ineffective hematopoiesis and susceptibility to transform to acute myeloid leukemia. The molecular pathways underlying disease initiation and evolution are still largely unknown. We recently demonstrated that acquired mutations in PTPN11 are a major event in JMML and occur with variable prevalence in children with other hematologic malignancies, including MDS.

Ineffective hematopoiesis linked with a mitochondrial tRNA mutation (G3242A) in a patient with myelodysplastic syndrome.

In a patient with refractory anemia with excess blasts (RAEB), a somatic mutation of mitochondrial transfer RNA(Leu(UUR)) was detected in bone marrow cells. Heteroduplex analysis indicated that 40% to 50% of mitochondrial DNA (mtDNA) molecules in the bone marrow (BM) carried the novel G3242A mutation. The proportion of mutant mtDNA was higher in CD34(+) cells than in the unfractionated sample.