Wolf-Karsten Hofmann

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Myelodysplastic syndromes and related disorders (myelodysplasia) are a heterogeneous group of myeloid neoplasms showing deregulated blood cell production with evidence of myeloid dysplasia and a predisposition to acute myeloid leukaemia, whose pathogenesis is only incompletely understood. Here we report whole-exome sequencing of 29 myelodysplasia specimens,(More)
Checkpoints that limit stem cell self-renewal in response to DNA damage can contribute to cancer protection but may also promote tissue aging. Molecular components that control stem cell responses to DNA damage remain to be delineated. Using in vivo RNAi screens, we identified basic leucine zipper transcription factor, ATF-like (BATF) as a major component(More)
Chronic myeloid leukemia (CML) is induced by the oncogenic BCR-ABL1 tyrosine kinase and can be effectively treated for many years with tyrosine kinase inhibitors (TKIs). However, unless CML patients receive life-long TKI treatment, leukemia will eventually recur; this is attributed to the failure of TKI treatment to eradicate leukemia-initiating cells(More)
Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR–ABL1 (ref. 1) and other oncogenic tyrosine kinases 2,3. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases 4,5. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs) 6–8 ,(More)
The Philadelphia chromosome (Ph) encoding the oncogenic BCR-ABL1 kinase defines a subset of acute lymphoblastic leukemia (ALL) with a particularly unfavorable prognosis. ALL cells are derived from B cell precursors in most cases and typically carry rearranged immunoglobulin heavy chain (IGH) variable (V) region genes devoid of somatic mutations. Somatic(More)
B cell lineage acute lymphoblastic leukemia (ALL) arises in virtually all cases from B cell precursors that are arrested at pre-B cell receptor-dependent stages. The Philadelphia chromosome-positive (Ph(+)) subtype of ALL accounts for 25-30% of cases of adult ALL, has the most unfavorable clinical outcome among all ALL subtypes and is defined by the(More)
Gene expression profiling has the potential to enhance current methods for the diagnosis of haematological malignancies. Here, we present data on 204 analyses from an international standardization programme that was conducted in 11 laboratories as a prephase to the Microarray Innovations in LEukemia (MILE) study. Each laboratory prepared two cell line(More)
The BCR-ABL1 kinase expressed in acute lymphoblastic leukemia (ALL) drives malignant transformation of human pre-B cells. Comparing genome-wide gene expression profiles of BCR-ABL1+ pre-B ALL and normal bone marrow pre-B cells by serial analysis of gene expression, many genes involved in pre-B cell receptor signaling are silenced in the leukemia cells.(More)
BACKGROUND For patients with locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is recommended as standard therapy. So far, no predictive or prognostic molecular factors for patients undergoing multimodal treatment are established. Increased angiogenesis and altered tumour metabolism as adaption to hypoxic conditions in cancers play an(More)
Imatinib is a novel tyrosine kinase inhibitor used for the treatment of Philadelphia chromosome-positive leukemias and other malignancies. Side effects are mostly moderate; however, a dose-dependent hematologic toxicity affecting all hematopoietic lineages is observed clinically. The aim of this study was to investigate the effect of imatinib on normal(More)