Showing papers by "Jana Markova published in 2009"

Monitoring of minimal residual disease in patients with core binding factor acute myeloid leukemia and the impact of C-KIT, FLT3, and JAK2 mutations on clinical outcome.

Abstract: Mutational analysis of C-KIT, fms-like tyrosine kinase 3 (FLT3), and JAK2 genes was performed in 60 patients with core binding factor acute myeloid leukemia (CBF-AML). Patients reaching molecular remission had lower incidence of relapse and better overall survival (OS) than those not achieving molecular remission (p = 0.008 and 0.044, respectively). The overall incidence of C-KIT mutations was 33.3%, FLT3/internal tandem duplication (ITD) 6.6%, FLT3(D835) 10.0% and JAK2(V617F) mutations 3.3%. C-KIT mutations did not predict for clinical/molecular relapse (p = 0.33). OS of patients with C-KIT mutations was identical to patients without them when all patients with CBF-AML were analyzed together (p = 0.58). When AML1/ETO-positive patients were evaluated separately, OS in C-KIT-mutated patients was slightly inferior to unmutated ones (p = 0.14). Patients with CBF-AML with a mutated C-KIT gene were also more prone to extramedullary disease (p = 0.08). Of six patients harboring various FLT3(D835) mutations, four (66.7%) relapsed, whereas among 43 cases without these mutations, 16 relapses (37%) were observed (p = 0.08). Our results on minimal residual disease, C-KIT, and FLT3/ITDs are in line with previous studies. Surprisingly, a possible role for FLT3(D835) mutations was noted in addition. These results need validation in even larger patient cohorts than ours. For routine clinical practice, it may be meaningful to screen for C-KIT mutations in AML1/ETO-positive patients, as well as for FLT3(D835) mutations in CBF-AML.

Eight cycles of BEACOPP escalated compared with 4 cycles of BEACOPP escalated followed by 4 cycles of BEACOPP baseline with or without radiotherapy in patients in advanced stage Hodgkin lymphoma (HL): Final analysis of the HD12 trial of the German Hodgkin Study Group (GHSG)

Abstract: 8544 Background: The GHSG HD9 trial had established BEACOPP escalated (BE) as new standard of care for advanced-stage HL patients. The successor study, HD12, evaluated a possible reduction in toxicity by comparing 8 cycles of BE with 4 cycles BE followed by 4 cycles BB. The second question in this trial related to the need of additional radiotherapy (RT) to initial bulk and residual disease. Methods: HL patients in stage IIB with large mediastinal mass and/or E-lesions or stage III/IV were randomised according to a 2x2-factorial design between: 8BE + RT, 8BE no RT, 4BE+4BB + RT, 4BE+4BB no RT. Primary endpoint of the trial was FFTF. Between 9/1999 and 1/2003, a total of 1,670 patients aged 16–65 were randomized. For this final analysis at a median follow up of 78 months, 99 patients were excluded for various reasons resulting in 1,571 eligible patients. Results: Patient characteristics in the 4 groups were comparable. Treatment-related toxicity of WHO grade III/IV was observed in 97% of patients. Most pro...

Nature of frequent deletions in CEBPA

Abstract: C/EBPalpha (CCAAT/enhancer binding protein alpha) belongs to the family of leucine zipper transcription factors and is necessary for transcriptional control of granulocyte, adipocyte and hepatocyte differentiation, glucose metabolism and lung development. C/EBPalpha is encoded by an intronless gene. CEBPA mutations cause a myeloid differentiation block and were detected in acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), multiple myeloma and non-Hodgkin's lymphoma (NHL) patients. In this study we identified in 41 individuals from 824 screened individuals (290 AML patients, 382 MDS patients, 56 NHL patients and 96 healthy individuals) a single class of 23 deletions in CEBPA gene which involved a direct repeat of at least 2 bp. These mutations are characterised by the loss of one of two same repeats at the ends of deleted sequence. Three most frequent repeats included in these deletions in CEBPA gene are CGCGAG (493-498_865-870), GCCAAGCAGC (508-517_907-916) and GG (486-487_885-886), all according to GenBank accession no. NM_004364.2. A mechanism for deletion formation between two repetitive sequences can be recombination events in the repair process. Double-stranded cut in DNA can initiate these recombination events of adjacent DNA sequences.