ASXL1 mutation as a surrogate marker in acute myeloid leukemia with myelodysplasia ‐related changes and normal karyotype

TheASXL1 mutation frequency is high in AML ‐MRC patients being its presence associated with specific characteristics, including morphological signs of dysplasia. This association raises the possible role ofASXL1 as a surrogate marker in AML ‐MRC, which could facilitate the diagnosis of patients within this group when the karyotype is normal, and especially when the assessment of multilineage dysplasia morphologically is difficult. This mutation could be used as a worst outcome marker in de novo AML‐MRC with intermediate‐risk kar yotype. AbstractAcute myeloid leukemia with myelodysplasia ‐related changes (AML‐MRC) are poor outcome leukemias. Its diagnosis is based on clinical, cytogenetic, and cytomorphologic criteria, last criterion being sometimes difficult to assess. A high frequency ofASXL1 mutations have been described in this leukemia. We sequencedASXL1 gene mutations in 61 patients with AML ‐MRC and 46 controls with acute myeloid leukemia without other specifications (AML‐NOS) to identify clinical, cytomorphologic, and cytogenetic characteristics associated withASXL1 mutational status. MutatedASXL1 (ASXL1+) was observed in 31% of patients with AML ‐MRC compared to 4.3% in AML‐NOS. Its presence in AML‐MRC was associated with older age, a previous history of myelodysplastic syndrome (MDS) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN), leukocytosis, presence of micromegakaryocytes in bone marrow, lower number of blasts in bone marrow,...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research

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AbstractPurpose of ReviewKnowledge of both somatic mutations and copy number aberrations are important for the understanding of cancer pathogenesis and management of myeloid neoplasms. The currently available standard of care technologies for copy number assessment such as conventional karyotype and FISH are either limited by low resolution or restriction to targeted assessment.Recent FindingsChromosomal microarray (CMA) is effective in characterization of chromosomal and gene aberrations of diagnostic, prognostic, and therapeutic significance at a higher resolution than conventional karyotyping. These results are compleme...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research
CONCLUSION: NGAL was related to neutrophil count and VEGF. NGAL and VEGF showed similar intergroup patterns, reflecting that NGAL was associated with VEGF. PMID: 32304694 [PubMed - as supplied by publisher]
Source: Clinical Biochemistry - Category: Biochemistry Authors: Tags: Clin Biochem Source Type: research
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: https://www.fightaging.org/newsletter/ Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Cells become senescent in response to a variety of circumstances. The vast majority are cases of replicative senescence, somatic cells reaching the Hayflick limit. Cell damage and toxic environments also produce senescence, and senescent cells are also created as a part of the wound healing process. A senescent cell ceases replication and begins to secrete inflammatory and pro-growth signals, altering the nearby extracellular matrix and behavior of surrounding cells - even encouraging them to become senescent as well. Near all senescent cells last a short time only, as they self-destruct or are removed by the immune...
Source: Fight Aging! - Category: Research Authors: Tags: Medicine, Biotech, Research Source Type: blogs
This study is registered with Clinicaltrials.gov, number NCT02560025, and has completed enrolment.FindingsBetween Dec 31, 2015, and Aug 1, 2017, we enrolled a total of 39 eligible patients. 19 (49%) of 39 patients had secondary acute myeloid leukaemia and three (8%) had therapy-related acute myeloid leukaemia. At mid-induction, 33 (85%) of 39 patients showed marrow aplasia, six (15%) received re-induction. The median follow-up was 13·7 months (IQR 12·7–14·4). Composite remission was 64% (two-stage 95% CI 48–79), with 20 (51%) of 39 patients achieving complete remission and five (13%) achiev...
Source: The Lancet Haematology - Category: Hematology Source Type: research
ogers Components of the pre-messenger RNA splicing machinery are frequently mutated in myeloid malignancies. Mutations in LUC7L2, PRPF8, SF3B1, SRSF2, U2AF1, and ZRSR2 genes occur at various frequencies ranging between 40% and 85% in different subtypes of myelodysplastic syndrome (MDS) and 5% and 10% of acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPNs). In some instances, splicing factor (SF) mutations have provided diagnostic utility and information on clinical outcomes as exemplified by SF3B1 mutations associated with increased ring sideroblasts (RS) in MDS-RS or MDS/MPN-RS with thrombocytosis. SF3...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Review Source Type: research
This study aimed to analyze the role of postoperative treatment for BC in the development of subsequent HM. Using the French National Health Data System, we examined the HM risks in patients diagnosed with an incident primary breast cancer between 2007 and 2015, who underwent surgery as first-line treatment for BC. Main outcomes were acute myeloid leukemia (AML), Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs), multiple myeloma (MM), Hodgkin’s lymphoma or non-Hodgkin’s lymphoma (HL/NHL), and acute lymphoblastic leukemia or lymphocytic lymphoma (ALL/LL). Analyses were censored at HM o...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
Conclusions The discovery of JAK2V617F mutation in BCR-ABL1-negative MPNs by four different international cooperative groups in 2005 (2–5) led to significant insights on the pathogenesis of these disorders. In fact, this mutation results in a gain-of-function with activation of cytokine and growth factor receptors, and thus of the downstream JAK-STAT pathway (79, 95–98). The JAK2 point mutation in exon 12, present in a small percentage of patients with PV, is able to induce the MPN phenotype through the same pathogenic mechanism (6, 7). In 2006 the MPLW515L/K was reported in ET and PMF patients (44, 45) and d...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
Somatic mutations in the additional sex combs like-1 (ASXL1) gene have been described in myeloid malignancies including acute myeloid leukemia (AML), myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML) and rarely in juvenile myelomonocytic leukemia (JMML). Most ASXL1 mutations occur in exon 13 (some time referred as exon 12) and are most often frameshift or nonsense mutations that result in C-terminal truncation of the protein upstream of the PHD finger region.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
In conclusion, 96.5% of patients with hematologic malignancies have adequate tissue for comprehensive genomic profiling. Most patients had unique molecular signatures, and 75% had alterations that may be pharmacologically tractable with gene- or immune-targeted agents.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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