China
Africa
Explore chapters and articles related to this topic
Familial Acute Myeloid Leukemia
Published in Dongyou Liu, Handbook of Tumor Syndromes, 2020
In contrast with germline-mutated CEBPA, AML arising in FPD/AML with mutated RUNX1 have an unfavorable prognosis [108], with hematopoietic stem cell transplant as the possible treatment to eradicate the mutant gene. Further, since only up to 60% of carriers with the germline RUNX1 mutation in FPD/AML families develop disease, and there is significant inter- and intrafamilial variation in the degree of disease penetrance, the risk of developing neoplasms (myeloid or lymphoid) cannot be predicted for carrier individuals in affected families. Since a subset of carriers have been shown to have earlyonset age-related clonal hematopoiesis, it has been suggested that monitoring of such clonal mutations may identify RUNX1 carrier individuals at higher risk for developing neoplasia [66]. The risk of progression in healthy carriers of DDX41 mutations is currently unknown. For healthy carriers in families with familial AML, uniform monitoring guidelines irrespective of genetic cause are recommended, including baseline bone marrow morphology examination and annual blood counts, with specific guidelines depending upon the clinical features of the germline genetic cause and in the familial presentation [110].
Vitamin C and Somatic Cell Reprogramming
Published in Qi Chen, Margreet C.M. Vissers, Cancer and Vitamin C, 2020
DNA hypermethylation has been well documented to cause silencing at the loci of tumor suppressor genes (reviewed by [144]) and is a hallmark of patients with myeloid malignancies such as MDS and AML [117,145]. TET2 mutations are associated with a DNA hypermethylation phenotype [117,146], an increased risk of MDS progression [147,148], and a poor prognosis in AML [141,149]. Studies of healthy aged individuals with clonal hematopoiesis (CH) have revealed that a disease-associated DNA methylation signature already exists in premalignant hematopoietic cells [150]. Epigenetic regulators such as DNMT3a and TET2 are the most frequently mutated genes in normal individuals with CH [125,151]. For TET2 mutant CH individuals, the ratio of 5 hmC to 5 mC has been shown to track with TET2 variant allele frequency, with higher mutant VAF leading to lower 5 hmC [150].
Acute Myeloid Leukemia
Published in Dongyou Liu, Tumors and Cancers, 2017
Clonal abnormalities may occur in normal individuals without evidence of a blood disorder. DNMT3A R882 mutations, which occur often in CN-AML, were most commonly identified in normal individuals—even in ages under 25 years—but with normally increased prevalence with age and having a low variant allele frequency of <3%. Because NPM1 mutations co-occur frequently with DNMT3A mutations in AML, NPM1 mutations appear to be closely related to the evolution of AML, with DNMT3A mutations possibly allowing the NPM1 mutant clones to be founded and expand toward AML. In addition, the presence of clonal hematopoiesis in normal individuals also has implications for the interpretation of mutational analysis findings in the clinical management of AML. Clonal hematopoiesis may also be detected in young, asymptomatic carriers of RUNX1 mutations, providing a possible biomarker in these families with high risk for development of AML.
Highly specific functional equivalence of XN-HPC for optimum CD34+ cell count in harvested allogeneic bone marrow stem cell products
Published in Hematology, 2022
Aisha Jamal, Tahir Khan, Uzma Zaidi, Quratul Ain Rizvi, Shafaq Jahanzeb, Ali Salim, Mehjabeen Imam, Tahir Shamsi
A limitation of this study is underrepresentation of adult bone marrow stem cells donors in both retrospective and prospective cohorts. Various non-HLA donor characteristics contribute to the overall outcome of HSCT. Of these, donor age has been postulated to be the most relevant factor influencing HSCT outcome. A survival advantage has been reported for recipients receiving a graft from younger donors in many unrelated donor (URD) studies [35–37]. The phenomenon of stem cell ageing has been addressed in this regard, and a cumulative decline in quality and function has been reported due to increased DNA damage [38]. Furthermore, clonal hematopoiesis also tends to increase with increasing age [39]. Keeping all of this in consideration, the result of our study will not be directly transferable/ applicable to adult bone marrow stem cell transplant donors. Focused studies on adult bone marrow stem cell donors will shed light on the utility of XN-HPC as a surrogate for CD34 + cells in adult stem cell donors.
Pathogenesis of aplastic anemia
Published in Hematology, 2019
Clonal hematopoiesis often manifests as somatic mutations. About one third of AA patients had mutations in candidate genes for MDS, AML, or both as determined using targeted deep-sequencing, SNP array karyotyping, or whole-exome sequencing. Yoshizato T et al. investigated 156 patients with AA using targeted sequencing and found that 36% of these patients had multiple somatic mutations ranging from 1 to 7 mutations. The majority of mutations were BCOR and BCORL1 (in 9.3% of patients), PIGA (in 7.5%), DNMT3A (in 8.4%), and ASXL1 (in 6.2%) [67]. Patients with PIGA, BCOR and BCORL1 mutations had a better response to IST, with improvements in progression free survival (PFS) and overall survival (OS). This implied a protective mechanism from immune-mediated destruction by pathogenic T cells [68,69]. However, patients with DNMT3A, ASXL1, JAK2/JAK3 or RUNX1 mutations had a poor response to IST and lower overall survival[70,71]. This suggests that monitoring clonal hematopoiesis and understanding the different types of mutations using deep sequencing and SNP array karyotyping are helpful to guide treatment strategies for AA patients.
Plasma DNA for early cancer detection – opportunities and challenges
Published in Expert Review of Molecular Diagnostics, 2019
Wai Kei Jacky Lam, Kwan Chee Allen Chan
Another issue of using plasma DNA analysis for cancer screening is the specificity of plasma DNA mutations for malignancies. Clonal hematopoiesis has been postulated to be one source of mutations in plasma DNA of apparently healthy individuals. It could be observed in up to 10% of people older than 65 years old [8]. Although clonal hematopoiesis predicts the future risk of hematological malignancies, most subjects with this age-related hematopoietic mosaicism do not develop into cancers in their lifetime. Sequencing of the white blood cells from the same individual may therefore be used for minimizing the false-positive screening results associated with mutations arising from clonal hematopoiesis.