Journal of the Association of Genetic Technologists最新文献

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.

Objectives: Noonan syndrome (NS) is a relatively common autosomal dominant disorder with characteristic features and molecular alterations. The most common recurrent alteration is in the PTPN11 gene, a proto-oncogene that encodes a cytoplasmic receptor tyrosine phosphatase and helps regulate kinase activity and control cell survival and replication. Mutations in this gene can increase the risk for the development of multiple different malignancies, particularly hematopoietic. Here we present a case of NS with a PTPN11 mutation demonstrating the classic presentation of Noonan syndrome as well as the expected clinical follow-up.

Objectives: We report a 74-year-old male whose bone marrow morphology, flow cytometry, MRI and serum electrophoresis showed evidence of plasma cell myeloma. Chromosome analysis of the bone marrow showed an abnormal karyotype, described as 51~53,XY,+3,+5,t(8;14)(q24 .1;q32),+9,+11,+15,+19,+21[cp6]/46,XY[14]. The t(8;14)(q24.1;q32) is mainly seen in Burkitt lymphoma but it can also be seen in plasma cell myeloma usually with the context of a complex karyotype. Based on the Mitelman database the involvement of C-MYC is usually seen in late tumor progression in plasma cell myeloma as a secondary rearrangement, usually during clonal evolution and divergence and is associated with a significantly decreased survival. Our case pinpoints the involvement of MYC abnormalities in plasma cell myeloma as well as the importance of cytogenetics as a tool to manage and monitor plasma cell myeloma cases.

Objectives: We report on a rare case of B-cell prolymphocytic leukemia (B-PLL) in a patient with a history of chronic lymphocytic leukemia (CLL) that showed a novel translocation t(10;22)(q21;q11.22) and an interstitial deletion of 11q14.1-q23.3 in 2017. The chromosome microarray analysis (CMA) confirmed the 11q22 deletion and revealed a small interstitial deletion of IGL gene. In 2018, the patient presented with worsening lymphocytosis, anemia and thrombocytopenia. The peripheral blood smear revealed an increased prolymphocyte population, which comprised 60.4% of lymphoid cells, establishing a diagnosis of B-cell prolymphocytic leukemia. The CMA and G-banded chromosome analysis showed one additional aberration in the form of 1q gain translocated onto the other homologue 22. These findings suggested clonal evolution of CLL to B-PLL. The most common translocation involving immunoglobulin lambda chain (IGL) in CLL is the t(18;22), followed by t(8;22) and (11;22). An evolution to B-PLL occurs in most cases without gaining additional aberrations. Here, we report for the first time a novel translocation involving IGL with chromosome 10q21 and one 1q gain occurring in a patient with CLL that transformed to B-PLL. Based on the disease progression and this newly developed cytogenetic aberration, our case supports the progressive nature of CLL in the presence of IGL deletion and suggests the pathological role of 1q gain in CLL transformation.

Objectives: Myelodysplastic syndromes present with a range of cytogenetic abnormalities that are used to guide diagnosis and management of the disease. Herein, we present the case of a 72-year-old female patient who presented with pancytopenia. Peripheral blood showed Hb 9.0 g/dl, neutrophils less than 1800/mm3, and platelets less than 100,000/mm3. Bone marrow showed erythroid hyperplasia, megaloblastic changes, dyserythropoiesis, multinuclearity, nuclear bridges, nuclear budding, atypical mitoses, and ring sideroblasts. Also, CD34 and CD117 as well as myeloperoxidase positive populations were present. On this basis, a diagnosis of myelodysplastic syndrome was rendered. Chromosome studies showed an abnormal female karyotype with an isochromosome 17q as well as deletion 20q in 17 of the 20 metaphase cells examined. The remaining three cells were cytogenetically normal. Molecular cytogenetic studies using a TP53-specific probe showed only one TP53 signal in 87% of the nuclei examined. An i(17q) as a sole cytogenetic aberration is rare among both MDS and myeloid malignancies in general, but is functionally similar to aberrations of 17p that lead to loss of TP53. This case provides further insight into the spectrum of cytogenetic abnormalities present in MDS.

Objectives: Whole-arm translocations are relatively rare among hematological malignancies. There are a few reports on der(18;21)(q10;q10). This is a recurrent but rare abnormality. Only about 11 cases harboring der(18;21)(q10;q10) have been reported. However, combined der(18;21) (q10;q10) and gain of chromosome 21 is even rarer, with only three cases reported. The previous cases were with AML, AML-M2, and aCML diagnosis. We report the first case of Ph-like, B-lymphoblastic leukemia (B-ALL) with +21 and der(18;21)(q10;q10) which resulted in loss of 18p and a gain of 21q. We address tumorigenesis and morphological characteristics of hematological malignancies involving der(18;21)(q10;q10), along with a review of the literature.

Objectives: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease caused by genetic abnormalities that manifest during the development of T-cell precursors, encompassing 15% of pediatric and 25% of adult ALL cases. While T-ALL and its heterogeneous genomic landscape has been well-characterized by establishing different subtypes and risk stratification for patients, the expression and activity of microRNAs (miRNAs) in T-ALL have not been investigated as extensively as cytogenetic and genomic abnormalities. miRNAs are prospective biomarkers that can be critical in improving diagnostic measures for T-ALL, expanding risk categorizations of patients for select therapies, and as target candidates for interventional treatments. Certain miRNAs have been found to be dysregulated as a result of mechanisms underlying T-ALL pathophysiology, including aberrant signaling pathways and epigenetics. Through the implementation of more robust bioinformatics such as miRNA target prediction tools, next-generation sequencing, and standard molecular techniques, recent research has underscored the significant contribution of miRNAs toward the development and progression of T-ALL by altering canonical signaling pathways associated with T-ALL such as NOTCH1, mTOR, and PI3K/AKT. In this review, we summarize the recent findings surrounding the expression and activity of dysregulated miRNAs and how they contribute to the onset and course of disease in T-ALL. As dysregulated miRNAs have been shown to elicit positive and negative responses, the dual effects of miRNAs demand additional research to elucidate miRNAs for target treatments in addition to profiling T-ALL further as a malignant disease.