The genetic abnormalities investigation of leukemia in past few decades

Cytogenetic and molecular analysis of each patient’s leukemia cells has become an essential component of diagnosis prior to treatment. It has furthered our understanding of leukemogenesis at a molecular level. Specific and well-characterized recurring chromosomal abnormalities facilitate diagnosis, confirm subtype classification, and have major prognostic value for treatment planning. Conventional chromosome analysis is a basic way for diagnosis and treatment. In addition in this way evaluation of disease progression is important and so it is the only method that can identify the presence of clonal evolution, particularly in accelerated and relapse phase in the disease. Also conventional cytogenetic can detect chromosomal abnormality associated with its advanced phase. Anyhow, the value of translocation rates in interphase and metaphase nuclei in monitoring leukemia is at the time of diagnosis and after treatment additionally. Genomic profiling transformed our understanding of the genetic basis of leukemia particularly in acute leukemia, which is a malignant clonal proliferation in lymphoid stem cells or myeloid progenitor cells.

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Clinical Application of Chromosomal Microarray Analysis for Fetuses with Craniofacial Malformations

10.21203/rs.3.rs-23063/v1 ◽

2020 ◽

Author(s):

Chenyang Xu ◽

Yanbao Xiang ◽

Xueqin Xu ◽

Lili Zhou ◽

Huanzheng Li ◽

...

Keyword(s):

Microarray Analysis ◽

Genetic Basis ◽

Chromosomal Abnormalities ◽

Chromosome Analysis ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Molecular Technique ◽

Craniofacial Malformations ◽

Pathogenic Cnvs ◽

Clinically Significant

Abstract Background This study aimed to evaluate the applicability of chromosomal microarray analysis (CMA) for prenatal diagnosis of craniofacial malformations (CFMs). We also investigated the potential correlations between chromosomal abnormalities and CFMs. To this end, 118 fetuses with CFMs were enrolled in the study and underwent both G-banded chromosome analysis and CMA. Results Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities or submicroscopic chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic CNVs only (10/118; 8.5%). We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes. Conclusion CMA is a rapid and reliable molecular technique to identify fetal chromosomal aberrations associated with CFMs. Identification of the genetic basis of CFMs contributes to the understanding of their pathogenesis and etiology.

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A microarray-komparatív genomhibridizálás (arrayCGH) praenatalis alkalmazása. Javaslat a hazai bevezetésre

Orvosi Hetilap ◽

10.1556/650.2019.31322 ◽

2019 ◽

Vol 160 (13) ◽

pp. 484-493

Author(s):

Zsolt Tidrenczel ◽

Erika P. Tardy ◽

Henriett Pikó ◽

Edina Sarkadi ◽

Ildikó Böjtös ◽

...

Keyword(s):

Clinical Utility ◽

Chromosomal Abnormalities ◽

Prenatal Testing ◽

Chromosome Analysis ◽

Molecular Karyotyping ◽

Chromosomal Microarray ◽

Comparative Genome Hybridization ◽

Genetic Abnormalities ◽

Array Comparative Genome Hybridization ◽

Copy Number Changes

Abstract: Invasive prenatal testing and conventional G-banding chromosome analysis have been considered to be the gold standard of fetal cytogenetic diagnosis. Standard karyotyping is, however, constrained by the limits of the resolution of using a microscope. The advantage of molecular karyotyping, array based methods is the evaluation of sub-microscopic copy number changes across the whole genome in a single analysis. The application of array comparative genome hybridization has greatly increased the detection of pathogenic chromosomal abnormalities in prenatal settings. Based on available data in the international literature of the last decade, the clinical utility of arrayCGH is the recognition of some 1–2% and 5–7% additional genetical information compared to metaphase karyotype alone in fetuses without ultrasound anomaly and in fetuses with ultrasonographically detected malformations, respectively. Thus arrayCGH improves the prenatal diagnosis of genetic abnormalities mainly in fetuses with structural sonographic findings. In the present paper we review the literature of chromosomal microarray and make a proposal for the application of the method in Hungarian prenatal genetical practice. Orv Hetil. 2019; 160(13): 484–493.

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Clonal Proliferation of Lymphoid and Myeloid Progenitor Cells in Patients with Hematological Abnormalities

Vox Sanguinis ◽

10.1159/000466891 ◽

1979 ◽

Vol 37 (2) ◽

pp. 84-88

Author(s):

Andrzej Górski ◽

Roma Robicka-Milewska ◽

Joanna Litwin ◽

Krystyna Kolakowska-Polubiec ◽

Kazimierz Madaliński

Keyword(s):

Progenitor Cells ◽

Clonal Proliferation ◽

Myeloid Progenitor ◽

Myeloid Progenitor Cells ◽

Hematological Abnormalities

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Clinical application of chromosomal microarray analysis for fetuses with craniofacial malformations

10.21203/rs.3.rs-23063/v2 ◽

2020 ◽

Author(s):

Chenyang Xu ◽

Yanbao Xiang ◽

Xueqin Xu ◽

Lili Zhou ◽

Huanzheng Li ◽

...

Keyword(s):

Microarray Analysis ◽

Genetic Basis ◽

Chromosomal Abnormalities ◽

Chromosome Analysis ◽

Copy Number Variations ◽

Chromosomal Microarray ◽

Chromosomal Microarray Analysis ◽

Phenotype Correlation ◽

Craniofacial Malformations ◽

Clinically Significant

Abstract Background: The potential correlations between chromosomal abnormalities and craniofacial malformations (CFMs) remain a challenge in prenatal diagnosis. This study aimed to evaluate 118 fetuses with CFMs by applying chromosomal microarray analysis (CMA) and G-banded chromosome analysis. Results: Of the 118 cases in this study, 39.8% were isolated CFMs (47/118) whereas 60.2% were non-isolated CFMs (71/118). The detection rate of chromosomal abnormalities in non-isolated CFM fetuses was significantly higher than that in isolated CFM fetuses (26/71 vs. 7/47, p = 0.01). Compared to the 16 fetuses (16/104; 15.4%) with pathogenic chromosomal abnormalities detected by karyotype analysis, CMA identified a total of 33 fetuses (33/118; 28.0%) with clinically significant findings. These 33 fetuses included cases with aneuploidy abnormalities (14/118; 11.9%), microdeletion/microduplication syndromes (9/118; 7.6%), and other pathogenic copy number variations (CNVs) only (10/118; 8.5%).We further explored the CNV/phenotype correlation and found a series of clear or suspected dosage-sensitive CFM genes including TBX1, MAPK1, PCYT1A, DLG1, LHX1, SHH, SF3B4, FOXC1, ZIC2, CREBBP, SNRPB, and CSNK2A1.Conclusion: These findings enrich our understanding of the potential causative CNVs and genes in CFMs. Identification of the genetic basis of CFMs contributes to our understanding of their pathogenesis and allows detailed genetic counselling.

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Clonal Proliferation of Lymphoid and Myeloid Progenitor Cells in Patients with Hematological Abnormalities

Vox Sanguinis ◽

10.1111/j.1423-0410.1979.tb02275.x ◽

1979 ◽

Vol 37 (2) ◽

pp. 84-88 ◽

Cited By ~ 2

Author(s):

Andrzej Górski ◽

Roma Rokicka-Milewska ◽

Joanna Litwin ◽

Krystyna Kolakowska-Polubiec ◽

Kazimierz Madaliński

Keyword(s):

Progenitor Cells ◽

Clonal Proliferation ◽

Myeloid Progenitor ◽

Myeloid Progenitor Cells ◽

Hematological Abnormalities

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Cytogenetic signatures of recurrent pregnancy losses

10.1101/2020.07.01.20144535 ◽

2020 ◽

Author(s):

Svetlana. A. Yatsenko ◽

Cristina Quesada-Candela ◽

Devereux N. Saller ◽

Stacy Beck ◽

Ronald Jaffe ◽

...

Keyword(s):

Genomic Instability ◽

De Novo ◽

Chromosomal Abnormalities ◽

Medical Center ◽

Clinical Care ◽

Chromosome Analysis ◽

Autosomal Aneuploidy ◽

Genetic Abnormalities ◽

Structural Chromosome ◽

Recurrent Pregnancy Losses

ABSTRACTObjectivesTo investigate the incidence of chromosomal abnormalities in the products of conception (POC) of patients with spontaneous miscarriages (SM) and with recurrent pregnancy losses (RPL), and to determine biological mechanisms contributing to RPL.DesignRetrospective cohort study.SettingUniversity-affiliated medical center.PatientsDuring a 20-years period, 12,096 POC samples underwent classical chromosome analysis as a part of standard clinical care.InterventionsCytogenetic findings were classified into six categories and compared between the SM and RPL cohorts.Main Outcome MeasuresRPL-specific cytogenetic abnormalities and sex bias in POCs with autosomal aneuploidy.ResultsAnalysis of a large cohort of RPL patients has identified an increased incidence of inherited and de novo structural chromosome abnormalities, recurrent polyploid conceptions, and complex mosaic alterations. These abnormalities are the signature of genomic instability, posing a high risk of genetic abnormalities to offspring independent of maternal age. Predominance of male conceptions in the RPL cohort points toward X-linked etiology and gender-specific intolerance for certain genetic abnormalities.ConclusionsOur study showed several possible genetic etiologies of RPL, including parental structural chromosome rearrangements, predisposition to meiotic nondisjunction and genomic instability in patients with karyotypically abnormal POCs. Loss of karyotypically normal fetuses might be attributed to defects in genes essential for fetal development and survival, as well as aberrations affecting the X chromosome structure or function. Molecular studies of parental and POC genomes will help to identify inherited defects in genes involved in meiotic divisions and DNA repair to confirm our hypotheses, and to discover novel fetal-essential genes.

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Minimal Toxicity to Myeloid Progenitor Cells of Weekly24-Hr Infusion of High-Dose 5-Fluorouracil: Direct Evidence from Colony Forming Unit-Granulocyte andMonocyte (CFU-GM) Clonogenic Assay

Pharmacology & Toxicology ◽

10.1034/j.1600-0773.2000.d01-22.x ◽

2000 ◽

Vol 86 (3) ◽

pp. 122-124 ◽

Cited By ~ 8

Author(s):

Kun-Huei Yeh ◽

Shiou-Hwei Yeh ◽

Yu-Shiahn Chang ◽

Ann-Lii ChengNote

Keyword(s):

Progenitor Cells ◽

Direct Evidence ◽

Clonogenic Assay ◽

High Dose ◽

Colony Forming Unit ◽

Minimal Toxicity ◽

Myeloid Progenitor ◽

Myeloid Progenitor Cells

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Clonal evolution and clinical implications of genetic abnormalities in blastic transformation of chronic myeloid leukaemia

Nature Communications ◽

10.1038/s41467-021-23097-w ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yotaro Ochi ◽

Kenichi Yoshida ◽

Ying-Jung Huang ◽

Ming-Chung Kuo ◽

Yasuhito Nannya ◽

...

Keyword(s):

Chronic Myeloid Leukaemia ◽

Myeloid Leukaemia ◽

Kinase Inhibitors ◽

Blast Crisis ◽

Clonal Evolution ◽

Chronic Phase ◽

Genetic Alterations ◽

Prognostic Impact ◽

Genetic Abnormalities ◽

Prior Use

AbstractBlast crisis (BC) predicts dismal outcomes in patients with chronic myeloid leukaemia (CML). Although additional genetic alterations play a central role in BC, the landscape and prognostic impact of these alterations remain elusive. Here, we comprehensively investigate genetic abnormalities in 136 BC and 148 chronic phase (CP) samples obtained from 216 CML patients using exome and targeted sequencing. One or more genetic abnormalities are found in 126 (92.6%) out of the 136 BC patients, including the RUNX1-ETS2 fusion and NBEAL2 mutations. The number of genetic alterations increase during the transition from CP to BC, which is markedly suppressed by tyrosine kinase inhibitors (TKIs). The lineage of the BC and prior use of TKIs correlate with distinct molecular profiles. Notably, genetic alterations, rather than clinical variables, contribute to a better prediction of BC prognosis. In conclusion, genetic abnormalities can help predict clinical outcomes and can guide clinical decisions in CML.

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