Sex chromosome changes in leukemia: cytogenetics and molecular aspects

Shahrabi, Saeid; Khodadi, Elahe; Saba, Fakhredin; Shahjahani, Mohammad; Saki, Najmaldin

doi:10.1080/10245332.2017.1375063

Cited by 15 publications

(9 citation statements)

References 62 publications

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“…present in approximately 6% of all male bone marrow karyotypes and in 16% of karyotypes from abnormal marrow 2,3 . The incidence of LOY in bone marrow cells increases proportionally with aging, with up to 20% of healthy men over 80 years of age showing LOY by conventional marrow karyotyping 4,5 .…”

Section: Introductionmentioning

confidence: 99%

“…LOY is observed in association with myeloproliferative neoplasms (MPN), myelodysplastic syndromes (MDS), acute myeloid leukemias (AML) and B-cell lymphomas/leukemias, often in the context of other chromosomal abnormalities 2,[6][7][8] . LOY is one of the most common recurrent cytogenetic abnormalities seen in MDS, with an incidence of up to 30% in males 3,5,[8][9][10][11][12][13] . The incidence of isolated LOY in MDS is lower, ranging from 4 to 10% 8,14 .…”

Section: Introductionmentioning

confidence: 99%

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Genomic alterations in patients with somatic loss of the Y chromosome as the sole cytogenetic finding in bone marrow cells

et al. 2020

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alterations in patients with somatic loss of the Y chromosome as the sole cytogenetic finding in bone marrow cells. AbstractLoss of the Y chromosome (LOY) is one of the most common somatic genomic alterations in hematopoietic cells in men. However, due to the high prevalence of LOY as the sole cytogenetic finding in the healthy older population, differentiating isolated LOY associated with clonal hematologic processes from aging-associated mosaicism can be difficult in the absence of definitive morphological features of disease. In the past, various investigators have proposed that a high percentage of metaphases with LOY is more likely to represent expansion of a clonal myeloid disease-associated population. It is unknown whether the proportion of metaphases with LOY is associated with the incidence of myeloid neoplasia-associated genomic alterations.To address this question, we identified marrow samples with LOY as isolated cytogenetic finding and used targeted next generation sequencing-based molecular analysis to identify common myeloid neoplasia-associated somatic mutations. Among 73 patients with median age of 75 years (range 29-90), the percentage of metaphases with LOY was <25% in 23 patients, 25-49% in 10, 50-74% in 8 and ≥ 75% in 32. A threshold of ≥ 75% LOY was significantly associated with morphologic diagnosis of myeloid neoplasm (p = 0.004). Further, ≥ 75% LOY was associated with a higher lifetime incidence of diagnosis of myelodysplastic syndromes (MDS; p < 0.0001), and in multivariate analysis ≥ 75% LOY was a statistically significant independent predictor of myeloid neoplasia [OR 6.17;; p = 0.0007]. Higher LOY percentage (≥75%) was associated with greater likelihood of having somatic mutations (p = 0.0009) and a higher number of these mutations (p = 0.0002). Our findings indicate that ≥ 75% LOY in marrow is associated with increased likelihood of molecular alterations in genes commonly seen in myeloid neoplasia and with morphologic features of MDS. These observations suggest that ≥ 75% LOY in bone marrow should be considered an MDS-associated cytogenetic aberration. Main manuscript

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genomic alterations in patients with somatic loss of the Y chromosome as the sole cytogenetic finding in bone marrow cells

et al. 2020

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“…The disease may be related to genetic, radiation, chemical substances, viral infection and other factors, which can lead to molecular alterations, such as gene mutation and chromosome rearrangements in the body ( 3 , 4 ). Accordingly, previous studies have revealed that the condition of leukemia may be associated with the high heterogeneity of cellular and molecular genetics; thus, chromosomal abnormalities and gene mutations are important prognostic indicators for patients with leukemia ( 5 , 6 ). In recent years, a number of studies have discovered that multiple long-chain non-coding RNAs (lncRNAs) are associated with the occurrence and development of leukemia, which may provide novel markers and targets for the diagnosis and therapy of leukemia ( 7 - 9 ).…”

Section: Introductionmentioning

confidence: 99%

Knockdown of SNHG16 suppresses the proliferation and induces the apoptosis of leukemia cells via miR‑193a‑5p/CDK8

Piao

Zhang

2020

Int J Mol Med

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Although small nucleolar RNA host gene 16 (SNHG16) is known to exhibit auxo-action in certain types of tumor, its role in leukemia remains unclear. The present study analyzed the role and mechanisms of action of SNHG16 in leukemia cells in order to identify therapeutic targets for this disease. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine SNHG16 expression in human leukemia cell lines. Using TargetScan 7.2 and dual-luciferase reporter assay, the target genes of SNHG16 were verified. Following the downregulation of the expression of SNHG16 or its target genes, Cell Counting kit-8 (CCK-8) assay was performed to examine the viability of the leukemia cells. In addition, flow cytometry was performed to analyze the cell apoptotic rates, and colony formation assays were used to determine the cell proliferative ability. RT-qPCR and western blot analysis were used to determine the association between SNHG16 and its target genes. SNHG16 was found to be abnormally highly expressed in acute myeloblastic leukemia cell lines, the knockdown of which weakened the viability of the leukemia cells, suppressed cell proliferation and promoted cell apoptosis. miR-193a-5p could bind to SNHG16, and its target gene was CDK8. Moreover, the expression of miR-193a-5p increased with the decrease in SNHG16 expression, while the inhibition of miR-193a-5p promoted the expression of CDK8. The downregulation of miR-193a-5p enhanced the viability of the leukemia cells, accelerated cell cloning and reduced cell apoptosis, which was completely opposite to the effects observed with the silencing of CDK8. The knockdown of SNHG16 suppressed the viability of the leukemia cells, suppressed cell proliferation, and induced cell apoptosis by regulating miR-193a-5p/CDK8. Thus, SNHG16 may prove to be a potential therapeutic target for the treatment of leukemia.

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“…By aging, somatic mutations accumulate in the cells, which can be an initiator of cancer. When hematopoietic stem cells (HSCs) acquire certain mutations they can expand a clone of leukocytes in blood circulation (Ebert & Libby, 2018;Jaiswal et al, 2014;Shahrabi, Khodadi, Saba, Shahjahani, & Saki, 2018). This premalignant state is referred to as clonal hematopoiesis of indeterminate potential (CHIP).…”

Section: Introductionmentioning

confidence: 99%

Clonal hematopoiesis: Genes and underlying mechanisms in cardiovascular disease development

Haybar

Shahrabi

Ghanavat

et al. 2018

Journal Cellular Physiology

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The clonal hematopoiesis when occurring without hematologic abnormalities is defined as clonal hematopoiesis of indeterminate potential (CHIP). Aging causes accumulation of somatic mutations, and hematopoietic stem cells (HSCs) can develop clonal expansion of different lineages by these mutations. CHIP has a correlation with cancer and cardiovascular disease (CVD) through acquired mutations in genes. DNMT3A, TET2, ASXL1, and JAK2 genes as well as other genes are the most common somatic mutations causing CHIP and CVD in an older age. Other factors such as cholesterol level, laboratory tests and indexes also affect CVD. In addition, mutations in adenosine triphosphate–binding cassette transporters and also chronic stress in nervous system can result in HSCs proliferation and CVD. However, laboratory tests and indexes are not sensitive for CVD diagnosis. But the therapeutic interventions can be helpful to prevent CVD cases by targeting somatic mutations, chemokine receptors, and growth factors in HSCs. Also, new drugs can control CVD by targeting of cells and their signaling pathways in HSCs. Therefore, more investigations are needed and more questions should be answered for the relationship between CHIP and CVD as a challenging issue in future.

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Sex chromosome changes in leukemia: cytogenetics and molecular aspects

Cited by 15 publications

References 62 publications

Genomic alterations in patients with somatic loss of the Y chromosome as the sole cytogenetic finding in bone marrow cells

Genomic alterations in patients with somatic loss of the Y chromosome as the sole cytogenetic finding in bone marrow cells

Knockdown of SNHG16 suppresses the proliferation and induces the apoptosis of leukemia cells via miR‑193a‑5p/CDK8

Clonal hematopoiesis: Genes and underlying mechanisms in cardiovascular disease development

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