Author
André Tichelli
Other affiliations: Leiden University, University of Pavia, University Hospital of Basel
Bio: André Tichelli is an academic researcher from University of Basel. The author has contributed to research in topics: Transplantation & Bone marrow. The author has an hindex of 30, co-authored 115 publications receiving 7218 citations. Previous affiliations of André Tichelli include Leiden University & University of Pavia.
Topics: Transplantation, Bone marrow, Aplastic anemia, Leukemia, Stem cell
Papers published on a yearly basis
Papers
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TL;DR: Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
Abstract: background Polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are clonal myeloproliferative disorders arising from a multipotent progenitor. The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that contributes to the cause of clonal expansion of hematopoietic cells in these diseases. methods We performed microsatellite mapping of the 9pLOH region and DNA sequencing in 244 patients with myeloproliferative disorders (128 with polycythemia vera, 93 with essential thrombocythemia, and 23 with idiopathic myelofibrosis). results Microsatellite mapping identified a 9pLOH region that included the Janus kinase 2 ( JAK2 )
3,391 citations
TL;DR: In this paper, the authors assessed the risk of cancer after aplastic anemia was treated with immunosuppression or bone marrow transplantation and sought to identify risk factors according to treatment.
Abstract: Background and Methods Recent studies have shown that long-term survivors of acquired aplastic anemia may be at high risk for malignant diseases. We assessed the risk of cancer after aplastic anemia was treated with immunosuppression or bone marrow transplantation and sought to identify risk factors according to treatment. The study population consisted of 860 patients treated by immunosuppression and 748 patients who had received bone marrow transplants for the treatment of severe aplastic anemia. The risk of cancer was analyzed overall and according to treatment relative to the risk in the general population. In calculating relative risk, we excluded patients with myelodysplastic syndromes or acute leukemias arising less than 6 months after treatment, and solid cancers arising less than 12 months after treatment, because of a possible association with aplastic anemia itself rather than with the treatment received. Results Forty-two malignant conditions were reported in the 860 patients who received immu...
430 citations
TL;DR: In a proportion of patients with MPDs, JAK2-V617F occurs on the background of clonal hematopoiesis caused by a somatic mutation in an as-yet-unknown gene.
283 citations
TL;DR: The incidence of late haematological complications in both groups of patients with severe aplastic anaemia in Basel from 1976 to 1986 is analysed.
Abstract: 137 patients with severe aplastic anaemia (SAA) were treated in Basel from 1976 to 1986. 34 underwent bone marrow transplantation (BMT) and 103 received antilymphocyte globulin (ALG) therapy. We have analysed the incidence of late haematological complications in both groups of patients.
20 patients treated with ALG developed a late haematological complication. A myelodysplastic syndrome or frank leukaemia occurred in eight and paroxysmal nocturnal haemoglobinuria (PNH) in 13 patients. Nine of the 13 patients with PNH had clinical signs of haemolysis, four only had positive laboratory tests. One patient had PNH and acute leukaemia. The risk of developing a haematological complication increased continuously and reached 57% at 8 years. Neither PNH nor leukaemia occurred in patients treated with BMT. The increased survival rate and the long observation time after ALG therapy have revealed a new perspective of the prognosis of aplastic anaemia. Patients treated with BMT appear to be cured whereas those treated with ALG remain at risk for late complications.
272 citations
TL;DR: The outcome of SAA patients has improved considerably over time and is influenced by patient variables such as severity of the disease and age, but also by the choice of the initial treatment, particularly first-line BMT from identical siblings.
252 citations
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TL;DR: The classification of myeloid neoplasms and acute leukemia is highlighted with the aim of familiarizing hematologists, clinical scientists, and hematopathologists not only with the major changes in the classification but also with the rationale for those changes.
4,274 citations
TL;DR: Genetic evidence and in vitro functional studies indicate that V617F gives hematopoietic precursors proliferative and survival advantages and a high proportion of patients with myeloproliferative disorders carry a dominant gain-of-function mutation of JAK2.
Abstract: background Polycythemia vera, essential thrombocythemia, and idiopathic myelofibrosis are clonal myeloproliferative disorders arising from a multipotent progenitor. The loss of heterozygosity (LOH) on the short arm of chromosome 9 (9pLOH) in myeloproliferative disorders suggests that 9p harbors a mutation that contributes to the cause of clonal expansion of hematopoietic cells in these diseases. methods We performed microsatellite mapping of the 9pLOH region and DNA sequencing in 244 patients with myeloproliferative disorders (128 with polycythemia vera, 93 with essential thrombocythemia, and 23 with idiopathic myelofibrosis). results Microsatellite mapping identified a 9pLOH region that included the Janus kinase 2 ( JAK2 )
3,391 citations
TL;DR: Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hematologic cancer and death.
Abstract: Cancers arise from multiple acquired mutations, which presumably occur over many years. Early stages in cancer development might be present years before cancers become clinically apparent. Methods We analyzed data from whole-exome sequencing of DNA in peripheral-blood cells from 12,380 persons, unselected for cancer or hematologic phenotypes. We identified somatic mutations on the basis of unusual allelic fractions. We used data from Swedish national patient registers to follow health outcomes for 2 to 7 years after DNA sampling. Results Clonal hematopoiesis with somatic mutations was observed in 10% of persons older than 65 years of age but in only 1% of those younger than 50 years of age. Detectable clonal expansions most frequently involved somatic mutations in three genes (DNMT3A, ASXL1, and TET2) that have previously been implicated in hematologic cancers. Clonal hematopoiesis was a strong risk factor for subsequent hematologic cancer (hazard ratio, 12.9; 95% confidence interval, 5.8 to 28.7). Approximately 42% of hematologic cancers in this cohort arose in persons who had clonality at the time of DNA sampling, more than 6 months before a first diagnosis of cancer. Analysis of bone marrow–biopsy specimens obtained from two patients at the time of diagnosis of acute myeloid leukemia revealed that their cancers arose from the earlier clones. Conclusions Clonal hematopoiesis with somatic mutations is readily detected by means of DNA sequencing, is increasingly common as people age, and is associated with increased risks of hematologic cancer and death. A subset of the genes that are mutated in patients with myeloid cancers is frequently mutated in apparently healthy persons; these mutations may represent characteristic early events in the development of hematologic cancers. (Funded by the National Human Genome Research Institute and others.)
2,497 citations
TL;DR: How cell-intrinsic changes in important structural cells can perpetuate the fibrotic response by regulating the differentiation, recruitment, proliferation and activation of extracellular matrix–producing myofibroblasts is described.
Abstract: Fibrosis is a key aspect of many chronic inflammatory diseases and can affect almost every tissue in the body. This review discusses recent advances in our understanding of the mechanisms of fibrosis, focusing on the innate and adaptive immune responses. It also describes how some of these crucial pathogenic pathways are being therapeutically targeted in the clinic.
2,492 citations
TL;DR: The understanding of the risk factors and causes of GHVD, the cellular and cytokine networks implicated in its pathophysiology, and current strategies to prevent and treat the disease are reviewed.
2,083 citations