Journal of the Association of Genetic Technologists最新文献

Objectives: A 67-year-old male patient was diagnosed with acute myeloid leukemia (AML) in April 2018. Chromosome analysis showed an abnormal male karyotype with an isodicentric chromosome 7q resulting in deletion 7q and two copies of 7p and a derivative chromosome 18 in 13 of the 20 metaphase cells examined. This karyotype was described as 46,XY,idic(7)(q11.2),der(18)t(1;18)(q23;q21.1)[13]/46,XY[7]. Additionally, subsequent sequencing analysis displayed FLT3-ITD and RUNX1 mutations (data not shown). The bone marrow showed an overwhelming number of blast cells, with co-expression of CD34, CD117, TdT, MPO, CD7, CD13, CD33, CD38, CD19, and HLA-DR. Molecular cytogenetic studies showed a deletion of one RELN/TES (7q22/7q31) signal in 80.5% of nuclei and a gain of a BCR/ABL1 (22q11.2/9q34) signal in 3.5% of interphase nuclei examined. These findings were described as nuc ish(RELN,TES)x1[161/200],(ABL1x2,BCRx3)[7/200], (EVI1,TAS2R1,EGR1,DEK,MYC,NUP214,KMT2A,DLEU1,DLEU2,Clone 163C9,PML,CBFB,RARA,PTPRT,MYBL2,RUNX1)x2[200]. The patient relapsed with AML in September 2019 and underwent treatment. However, all AML treatment options were exhausted by March 2020. An isodicentric chromosome 7 leading to two copies of the short arm of chromosome 7 (7p) and deletion 7q is a rare event in AML and is rarely described in the literature. The key element here is that this specific rearrangement leads to deletion 7q which is a well-known abnormality in AML that places the patient in the Poor/Adverse risk category.

Objectives: Ring chromosomes, which are formed through the fusion of the telomeric ends of a chromosome, present with a spectrum of symptoms whose severity depends on the amount of genetic material lost. Ring chromosome 13 cases present with symptoms similar to that of deletion 13q syndrome, and can be classified depending on whether several critical regions are involved in the deletion. An important region to consider is locus 13q32, whose deletion is known to cause severe phenotypes and major malformations. In contrast, deletions of the more distal locus 13q34 have been shown to be involved in symptoms such as microcephaly and ambiguous genitalia. Herein, we report a case of a pediatric patient with r(13) who presented with microcephaly, facial dysmorphism, hand and feet anomalies, and ambiguous genitalia. The karyotype was described as 46,XY,r(13)(p11.1q34). This case highlights the importance of cytogenetic analysis in determining the prognostic implications of ring chromosome cases.

Objectives: The ASXL1 (additional sex combs like 1) gene on 20q11 codifies the ASXL1 protein that belongs to protein complexes that play a role in gene expression and epigenetic regulation. ASXL1 is located near the DNMT3B gene and is part of a family of three genes (ASXL1, ASXL2, ASXL3) that are homologues to the Drosophila Asx gene. The ASXL1 gene contains a total of 14 exons and is expressed in the vast majority of hematopoietic cell types. While the specific job of ASXL1 in normal hematopoiesis and the involvement of mutated ASXL1 to the progression of hematopoietic malignancies have not yet been fully set forth, current data studies propose that ASXL1 is characterized as a tumor suppressor gene. Mutations in the ASXL1 gene are observed in myeloid malignancies usually associated with aggressiveness and poor clinical results and were reported first in the year 2009 in myelodysplastic syndromes (MDS). Nevertheless, ASXL1 gene mutations are also found in acute myeloid leukemia (AML) with normal karyotype as well as AML with myelodysplasia-related changes and AML with non-characteristic cytogenetic findings. Herein we examine the involvement of the ASXL1 gene in AML to address the importance of these ASXL1 mutations in the prognostic evaluation of AML.

Objectives: The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system is an RNA-guided DNA targeting platform widely known for its application in genome editing. Originally derived from the bacterial and archaebacterial defense mechanism against phage infection, it has since been studied and utilized for its potential as a genetic engineering tool and as a therapeutic agent. The Cas9 protein in its standard form induces double-stranded breaks (DSBs) in the target dsDNA sequence; however, modifications of the Cas9 protein have allowed for single-stranded breaks (SSBs) and even epigenetic modifications of gene expression. In comparison with previous methods including RNA interference, Zinc Finger Nucleases, and TAL Effector Nucleases, CRISPR is cheaper, more easily customized, and has a higher fidelity to its target site with fewer off-target effects. Consequently, CRISPR has become a central gene editing technique in a broad variety of research settings, with great potential for applications in human health. In this review, we offer an overview of CRISPR's mechanism of action and recent advancements in the application of CRISPR, as well as discuss literature pertinent to CRISPR applications to human health including many exciting prospective treatments for serious pathologies.

Objectives: Acute myeloid leukemia may present with significant dysmyelopoiesis within the peripheral blood smear and bone marrow aspirate. In the setting of Vitamin B12 deficiency, proliferation of a clonal population of malignant cells can become impaired, masking an underlying myelodysplastic or leukemic process. Typically, the cautionary tale warns against diagnosing acute myeloid leukemia before ruling out Vitamin B12 deficiency. Here we describe a patient who initially presented with pancytopenia and Vitamin B12 deficiency who, upon supplementation, developed overt acute myeloid leukemia. This case will highlight the importance of cytogenetic and molecular studies as essential diagnostic tools in patients with unique presentations.

Objectives: A 19-year-old male with a history of irritable bowel syndrome presented with progressive fatigue, periorbital petechiae, and abdominal pain for 2-3 weeks. The peripheral blood smear showed leukocytosis and circulating blasts. Elevated PT, PTT, and FDP with normal fibrinogen were found in the DIC panel workup. Abdominal CT suggested splenomegaly. A bone marrow biopsy revealed sheets of monotonous agranular monoblasts nearly completely replaced the hematopoietic elements. Chromosome analysis depicted an abnormal male karyotype with a t(9;11)(p22;q23) in all metaphase cells examined. Four cells showed, in addition, two 8q isochromosomes. FISH analysis was utilized with the MYC (8q24.21) probe from Abbott and the KMT2A (11q23), those of which showed gain on MYC and evidence of KMT2A. These findings correlate with the concurrent conventional cytogenetic findings and were described as nuc ish(MYCx4~9)[182/200],(KMT2Ax2)(5'KMT2A sep 3'KMT2Ax1)[181/200]. Complex karyotypes are associated with poor prognosis. Although only a few pediatric cases exist in the literature, the presence of additional abnormalities put this finding as a poor prognostic marker in AML. Correlation with other clinical data was indicated.

Objectives: Optical Genome Mapping (OGM) has emerged as a very powerful technology to diagnose in a single step a large variety of chromosomal abnormalities with high accuracy, at an unprecedented resolution, and in a time- and cost-effective way. A few recent studies provided a proof-of-principle that OGM can replace traditional cytogenomic assays (karyotyping, FISH, and SNP-arrays) in constitutional studies and the evaluation of hematologic disorders. OGM not only identified abnormalities previously diagnosed by standard methods, it highlighted the structural complexity of some rearrangements and uncovered novel findings with potential diagnostic, prognostic and therapeutic significance. While OGM still seems to have some technical and diagnostic limitations that require fine-tuning and improvement, it has so far shown so many promising advantages that future routine use heralds a revolutionary era in next-generation cytogenomic analysis.Keywords: Optical Genome Mapping, cytogenetic diagnosis, chromosome abnormalities detection, cancer cytogenetics, constitutional chromosome aberrations, cytogenomic variation, structural variants (SVs), copy number variants (CNVs)

Objectives: Atypical chronic myeloid leukemia, BCR-ABL1-negative (aCML), is a rare myelodysplastic/myeloproliferative neoplasm with heterogeneous clinical and genetic features, a high rate of transformation to acute myeloid leukemia (AML), and poor survival rate. The diagnosis of aCML is a diagnosis of exclusion and requires the fulfillment of strict diagnostic criteria. Until recently, there were no distinctive cytogenetic or molecular abnormalities for aCML adding to the diagnostic challenge. We present a case of aCML and highlight the pertinent clinical, morphological, and genetic features required for the diagnosis.

Objectives: Monoclonal B-cell lymphocytosis (MBL) is a light-chain restricted proliferation of mature B cells fewer than 5000 cells/μL without additional clinical or hematologic abnormalities. Sibling studies of individuals genetically susceptible to chronic lymphocytic leukemia (CLL) first identified monoclonal B cells in otherwise healthy persons, and studies show a 3% to 14% prevalence for MBL in persons over 40 years of age. Non-CLL-type MBL accounts for less than 20% of all MBL cases, and its progression is incompletely characterized. Here we present the case of an 85-year-old man with CD5-, CD19+, CD20 bright, and lambda-restricted lymphoid cells whose immunophenotypic findings are suggestive for a precursor lesion to marginal zone lymphoma (MZL). Karyotyping showed monosomy 21 without additional cytogenetic changes in three of the 35 cells examined. Monosomy 21 as a sole abnormality in CLL has been detected in just 11 cases between 1984 and 2003. As a sole abnormality in splenic and nodal marginal zone lymphoma, only three instances of monosomy 21 have been recorded on the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer. The significance of monosomy 21 as a marker for oncogenesis remains unclear.

Objectives: Objective: Host genetics can influence susceptibility to Chlamydia trachomatis infection. This study examined two genetic variants in human protein disulfide isomerase A2 (PDIA2), a member of a family of protein chaperones that participate in the chlamydial life cycle. Methods: A total of 278 male and female subjects, positive or negative for C. trachomatis infection, were genotyped for PDIA2 polymorphisms (rs400037 and rs419949) using real-time PCR and pyrosequencing. Results: There was a significant odds ratio of 8.21 (95% CI: 1.77-38.16) for rs400037 and 9.89 (95% CI: 1.19-82.10) for rs419949, for the AA genotypes. Conclusion: This indicates that individuals with the PDIA2 AA genotypes have significantly increased susceptibility to C. trachomatis infection as compared to the other PDIA2 genotypes (GG, GA). This correlation may be explained by an interactive role of host protein disulfide isomerases in the attachment and entry of C. trachomatis into cells.