Summary:Keywords: AML; inv(16); CBF/MYH11; MRD; BMTWe evaluated the occurrence of the CBF/MYH11 fusion transcripts by PCR analysis in 10 patients with Acute myelomonocytic leukemia with bone marrow eosinoinv(16)(p13;q22) acute myeloid leukemia (AML) who philia (AML-M4Eo), according to the French-Americanunderwent allogeneic bone marrow transplantation British (FAB) classification, is a distinct subtype of AML. (BMT) (n = 5), peripheral blood progenitor cell trans-AML-M4Eo is often associated with rearrangements of plantation (PBPCT) (n = 3), or autologous transplanchromosome 16, mostly involving 16p13 and 16q22, leadtation (n = 2). In addition to the analysis of minimal ing either to a pericentric inversion, inv(16)(p13q22) or, residual disease (MRD), the chimerism status of patients less commonly, to a translocation between the homologous after allogeneic transplant was studied by PCR. The chromosomes, t(16;16)(p13;q22). The pericentric inversion CBF/MYH11 fusion trancript was not detectable in six inv(16)(p13q22) is one of the most frequently occurring of seven patients who remained in remission after allochromosomal rearrangements detected in this neoplasm, geneic BMT or PBPCT. Two of these patients in which has been reported to account for approximately 16% remission were monitored for 50 months and 64 months of all AML. undergo allogeneic BMT have a significantly lower risk of transcript was detectable. In one patient in relapse, the relapse than their counterparts treated with chemotherapy fusion transcript was not only detectable in blood and alone. On the other hand allogeneic BMT is associated with bone marrow, but also in a cerebrospinal fluid sample more treatment-related mortality than autologous BMT or prior to transplant. Two patients who received autologchemotherapy alone. ous BMT were monitored for CBF/MYH11 transcripts Several reports suggest that the CBF/MYH11 fusion 3 months after BMT. The CBF/MYH11 was detected mRNA can often be detected in patients in long-term in these patients. Both patients subsequently relapsed 3 remission after chemotherapy. [4][5][6][7] To date, other than single months and 23 months post-autologous BMT. The case reports, studies of the detection of the CBF/MYH11 results study show that analysis of the CBF/MYH11 fusion transcripts after allogeneic BMT do not exist. institution. In addition to the analysis of minimal residual Germany
Clonal hematopoiesis (CH) is common among older people and associated with an increased risk of atherosclerosis, inflammation, and shorter overall survival. Age and inflammation are major risk factors for ischemic stroke, yet the association of CH with risk of secondary vascular events and death is unknown. We investigated CH in peripheral blood DNA from 581 patients with first-ever ischemic stroke from the Prospective Cohort with Incident Stroke-Berlin study (PROSCIS-B) using error-corrected targeted sequencing. The primary composite endpoint (CEP) consisted of recurrent stroke, myocardial infarction, and all-cause mortality. 348 somatic mutations with a variant allele frequency ≥ 1% were identified in 236/581 patients (41%). CH was associated with large-artery atherosclerosis stroke (P = 0.01) and white matter lesion (P < 0.001). CH-positive patients showed increased levels of pro-inflammatory cytokines such as IL-6, IFN-γ, hsCRP, and VCAM-1. CH-positive patients had a higher risk for the primary CEP (HR: 1.55, 95%-CI 1.04 - 2.31, P = 0.03), which was more pronounced in patients with larger clones. CH clone size remained an independent risk factor (HR 1.30, 95%-CI 1.04 - 1.62, P = 0.022) in multivariable Cox regression. While our data show that in particular larger and TET2- or PPM1D-mutated clones are associated with increased risk of recurrent vascular events and death, this risk is partially mitigated by a common germline variant of the IL-6 receptor (IL-6R p.D358A). The CH mutation profile is accompanied by a pro-inflammatory profile opening new avenues for preventive precision medicine approaches to resolve the self-perpetuating cycle of inflammation and clonal expansion.
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