Ruby Tang, Amy Cheng, Fabian Guirales, Wilson Yeh, Carlos A Tirado
{"title":"c-MYC Amplification in AML.","authors":"Ruby Tang, Amy Cheng, Fabian Guirales, Wilson Yeh, Carlos A Tirado","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>Acute myeloid leukemia (AML) is a clonal disorder of myeloid lineage precursors. Identification of cytogenetic aberrations is essential for classification and risk stratification of AML, with many demonstrating unique associations with various clinicopathologic features. One such abnormality is MYC amplification, a rare occurrence identified in less than 1% of AML patients. MYC is most commonly amplified in the form of double minutes, but may also occur via ring and marker chromosomes or homogeneously staining regions. Amplification of MYC often involves various chromosomal aberrations, including trisomies 4 and 6 and aneusomy of the sex chromosomes. In many cases, the presence of MYC amplicons is also associated with other negative prognostic factors, including complex karyotype and advanced age. Although MYC has been extensively investigated as a therapeutic target in various cancers, there are few studies examining the clinical significance of MYC amplification in AML. In this review, we explore recurrent cytogenetic abnormalities and demographic characteristics associated with amplification of MYC in patients with AML and discuss their diagnostic and therapeutic implications.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39829573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Unintended Consequences: Therapy-Related Acute Myeloid Leukemia.","authors":"Kayla Elliott, Katherine Devitt, Juli-Anne Gardner","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>Acute myeloid leukemia (AML) is a group of diseases resulting from a clonal expansion of myeloid precursor cells in the bone marrow. Each subtype harbors characteristic clinical, morphologic, and molecular features. AML is most often de novo and arises from somatic mutations causing unchecked proliferation of myeloblasts, but it may also present as a secondary malignancy, often as the result of prior cytotoxic exposure. Here we present a case of therapy-related AML (t-AML) following chemotherapy exposure found to have a characteristic balanced translocation involving 11q23 and outline a potential mechanism of oncogenesis.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39243711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anna Okabe, Fabian Guirales, Diane Zhao, Carlos A Tirado
{"title":"FLT3 Gene Involvement in B-cell Acute Lymphoblastic Leukemia (B-ALL).","authors":"Anna Okabe, Fabian Guirales, Diane Zhao, Carlos A Tirado","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>The FMS-like tyrosine kinase 3 gene (FLT3) is a receptor tyrosine kinase expressed in early hematopoietic progenitors that play an important role in hematopoietic development. The signaling pathways that are stimulated by the FLT3 protein manage several crucial cellular processes including division, growth, and survival of cells, specifically of hematopoietic progenitor cells. Activating mutations of this gene have been highly discussed in myeloid malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, FLT3 mutations are also observed in around 5% of acute lymphoblastic leukemia (ALL) patients. These mutations were usually found to be one of the four types: internal tandem duplications, tyrosine kinase domain mutations, juxtamembrane insertion and deletion, and juxtamembrane point mutation. The presence of FLT3 mutations in pediatric B-ALL patient populations tend to be associated with relapse and poor prognosis. These mutations are also correlated with poor prognosis in adult B-ALL patients. Due to the rarity of FLT3 mutations in B-ALL patients, there have been many challenges in attempts to understand their role in pathogenesis. In this review, we will discuss the most recent literature and trends associated with FLT3 mutations in B-ALL patients in order to elucidate their cytogenetic, molecular, and clinical implications.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25448655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Anne Okabe, David Palencia, David Trejo-Solis, Alberto Duarte-Martinez, Angélica López-Bernal, Lorena Villalba Salgado, Félix Labán, Carlos A Tirado
{"title":"A Case Study of Ring Chromosome 13 in a Pediatric Patient.","authors":"Anne Okabe, David Palencia, David Trejo-Solis, Alberto Duarte-Martinez, Angélica López-Bernal, Lorena Villalba Salgado, Félix Labán, Carlos A Tirado","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39242278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Catherine Gereg, Joanna L Conant, Sakshi Jasra, Katherine A Devitt, Juli-Anne Gardner
{"title":"Acute Myeloid Leukemia with Myelodysplasia-Related Changes Presenting as Vitamin B12 Deficiency: A Cautionary Tale.","authors":"Catherine Gereg, Joanna L Conant, Sakshi Jasra, Katherine A Devitt, Juli-Anne Gardner","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39829575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carlos A Tirado, Leena Nabipur, Joy King, Anna Okabe, Fabian Guirales, M Teresa Guardiola, Krystal Eastwood, William Koss
{"title":"A t(9;11)(p22;q23) Within the Context of a Complex Karyotype is Associated with a Poor Prognosis in a 19-Year-Old Patient with AML.","authors":"Carlos A Tirado, Leena Nabipur, Joy King, Anna Okabe, Fabian Guirales, M Teresa Guardiola, Krystal Eastwood, William Koss","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39243709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Optical Genome Mapping: A Revolutionary Tool for \"Next Generation Cytogenomics Analysis\" with a Broad Range of Diagnostic Applications in Human Diseases.","authors":"Jaime Garcia-Heras","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>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.\u0000\u0000Keywords: Optical Genome Mapping, cytogenetic diagnosis, chromosome abnormalities detection, cancer cytogenetics, constitutional chromosome aberrations, cytogenomic variation, structural variants (SVs), copy number variants (CNVs)</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39716856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Solving the Puzzle: The Diagnosis of Atypical Chronic Myeloid Leukemia, BCR-ABL1-Negative (aCML).","authors":"Karamatullah Danyal, Katherine Devitt, Juli-Anne Gardner","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39391697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wilson Yeh, Dariusz Mrugala, Hannah Robinson, Carlos A Tirado
{"title":"Monosomy 21, a Sole Abnormality in an Elderly Man with Non-CLL-Type Monoclonal B-cell Lymphocytosis.","authors":"Wilson Yeh, Dariusz Mrugala, Hannah Robinson, Carlos A Tirado","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39829574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Christopher Zysk, Steven Williams, Itzel Chavarria, Hailey Wilson, Adedayo Balogun, Emily Jacobs, Rachel Kaminski, Baru-Ta Foma, Jack Johnson, Wesley Lux, Kristyn McCoy, Stephen Morales, Gina Sanchez, Paul Grubb, Melanie Littlejohn, Ryan Mize, Jorge Moreno, Caryn Pirtle, Ericka C Hendrix, Katie M Bennett
{"title":"Genetic Variants in Host Protein Disulfide Isomerase 2 (PDIA2) are Associated with Susceptibility to Chlamydia Trachomatis Infection.","authors":"Christopher Zysk, Steven Williams, Itzel Chavarria, Hailey Wilson, Adedayo Balogun, Emily Jacobs, Rachel Kaminski, Baru-Ta Foma, Jack Johnson, Wesley Lux, Kristyn McCoy, Stephen Morales, Gina Sanchez, Paul Grubb, Melanie Littlejohn, Ryan Mize, Jorge Moreno, Caryn Pirtle, Ericka C Hendrix, Katie M Bennett","doi":"","DOIUrl":"","url":null,"abstract":"<p><strong>Objectives: </strong>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.</p>","PeriodicalId":73975,"journal":{"name":"Journal of the Association of Genetic Technologists","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38351590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}