Journal of the Association of Genetic Technologists最新文献

Objectives: Acute myeloid leukemia (AML) is a heterogeneous disease, indicated by its many conceivable cytogenetic mutations. Hyperdiploidy is a rare abnormality in AML, more prevalent in children than adults, with few other distinguishing associations. Chromosome totals above 49 in AML are very rare (2%). AML with hyperdiploidy can first be categorized as low or high hyperdiploidy (HH) based on modal chromosome number. High hyperdiploidy is then subcategorized into adverse, structural, or numerical HH. Across all three subtypes of HH, gains of chromosomes 8, 13, and 21 are the most frequent. Although the general survival outcomes of HH AML have remained inconsistent across several different studies, prognosis often relies on the modal chromosome number of the patient, with higher numbers having significantly poorer overall survival rates (OS). Here, we present an 80-year-old male patient with AML showing an abnormal karyotype presenting 78 to 81 chromosomes.

Objectives: IgD myeloma is a rare subset of multiple myeloma characterized by the production of monoclonal IgD protein. This subset of myeloma generally has a more severe and aggressive clinical course. The case reported here is of a 61-year-old female with recurrent disease complicated by encephalopathy, myalgia, and extensive skeletal involvement. The bone marrow showed sheets of plasma cells and plasmablasts, with flow cytometry demonstrating a monoclonal population of CD138-positive, lambda-restricted cells. FISH demonstrated a t(11;14)(q13;q32) translocation and a gain of 1q. Despite treatments with daratumumab, bortezomib, lenalidomide, dexamethasone, and autologous stem cell transplant, the patient ultimately expired from streptococcal pneumonia with hypoxic respiratory and subsequent multiorgan failure.

Objectives: The Nobel Assembly of the Karolinska Institute (Sweden) awarded the 2024 Nobel Prize in Physiology or Medicine to Dr. Victor Ambros (University of Massachusetts Chan Medical School, Worcester, United States) and Dr. Gary Ruvkun (Massachusetts General Hospital, Boston, United States). This award recognized their joint discoveries of microRNAs and a novel mechanism of post-transcriptional regulation of gene expression in the worm C. elegans. This revolutionary breakthrough demonstrated first that miRNAs provide a refined control of development in C. elegans targeting mRNAs from distinct genes in an orderly fashion. Subsequent discoveries of many more microRNAs in other organisms across a wide evolutionary tree showed that these molecules and the regulatory mechanism of gene expression that they regulate are conserved throughout evolution. With more studies, these advances also triggered a realization that microRNAs play important roles in various critical biological processes (e.g., cellular growth, differentiation, development, cellular physiology, etc.). Other surveys reported abnormalities in microRNAs connected to multiple human diseases which, in turn, generated research interest in potential treatments focused on faulty microRNAs and their evaluation as potential markers of disease. This Nobel Prize caps nearly three decades of unprecedented advances in RNA research that include similar awards. A 2006 Nobel Prize honored the discovery of RNA interference that was initially described in 1998. The 2023 Nobel Prize paid tribute to the first effective human mRNA vaccines. Both advances generated practical applications of high significance including medical uses in humans. For these reasons, there is hope that in due time it will also be the case with microRNAs given their biological potential and many relevant physiological functions that they control.

Objectives: The Nobel Prize in Physiology or Medicine for 2023 awarded to Dr. Katalin Karikó and Dr. Drew Weissman recognized their seminal discoveries in nucleoside modifications of messenger RNA that were pivotal to developing the first mRNA vaccines for clinical use in humans. These novel vaccines were key for prophylactic control of a pandemic caused by the new coronavirus SARS-CoV-2 that emerged abruptly in late 2019/early 2020. This breakthrough capped years of previous research in coronaviruses that included SARS- CoV and MERS-CoV associated with earlier human outbreaks, developments of more efficient formulations to deliver nucleic acids in vivo, and applications of a novel mRNA technology to generate a new generation of better vaccines cost-effectively. Such successful outcomes herald a wide range of advances with this highly adaptable mRNA technology. These include vaccines against existing infectious agents of medical significance but also emerging pathogens, cancer immunotherapies, and protein-replacement therapies, while at the same time, other uses are also under active investigation.

Objectives: Acute myeloid leukemia, myelodysplasia-related (AML-MR) is a particularly aggressive and adverse subtype of acute myeloid leukemia, predominantly affecting older adults who often face complex treatment challenges and poor prognoses. The majority of AML-MR patients fail to achieve remission, leading to significantly reduced overall survival rates. In light of these dire outcomes, staying informed about the most recent advancements in AML-MR research and clinical practice is imperative. This review examines the latest World Health Organization classifications of AML-MR, highlighting this disease's prevalent mutations and cytogenetic abnormalities. Furthermore, we explore recent therapeutic developments, including the introduction of targeted therapies and hypomethylating agents, which offer promising avenues for improving patient outcomes. The reclassification of AML-MR underscores the critical role of genetic profiling in elucidating its pathology and guiding therapeutic strategies. Future research should focus on developing personalized treatment approaches that address the intricate genetic and clinical complexities of AML-MR, aiming to enhance survival rates and improve the quality of life for affected patients.

Objectives: We report a 76-year-old male patient with myelodysplastic syndrome (MDS) with a t(9;22) and deletion 20q only by FISH. Past medical history is significant for prostate cancer status post radiation therapy and a 28-pack-year smoking history. In 2016, the patient developed a DVT and incidentally was found to have a BCR::ABL1 (p210) by PCR analysis (level of 0.54% of the international scale). Subsequent bone marrow aspiration revealed a hypercellular bone marrow with a small monoclonal B-cell population morphologically consistent with chronic myelogenous leukemia (CML). FISH analysis demonstrated t(9;22) translocation and a loss of 20q12 in 5% of nuclei. The patient was started on nilotinib therapy. Follow-up BCR::ABL1 testing six months later did not detect BCR::ABL1; however, subsequent FISH analysis on bone marrow aspirates performed at one and seven years after initial diagnosis continued to show deletion 20q (1-3% of nuclei). Morphologic features of bone marrow aspirates have demonstrated a CML-type hypercellular bone marrow with myeloid/megakaryocytic hyperplasia and micromegakaryocytes. This case pinpoints the importance of comprehensive study when MDS is present with deletion 20q and a t(9;22), as it can be misdiagnosed as CML. While definitive therapeutic guidelines have yet to be established for this rare presentation of MDS, the use of tyrosine kinase inhibitors is under investigation.

Objectives: Two recent studies that re-examined through novel approaches previous shotgun sequencing data from prehistoric/historic Europeans uncovered several autosomal and sex chromosome aneuploidies (Anastasiadou et al., 2024; Rohrlach et al., 2024). These disorders, which are common in contemporary humans, were trisomies 18 and 21, Klinefelter syndrome (47,XXY), 47,XYY syndrome, and mosaic Turner syndrome X/XX. These discoveries about prehistoric/historic occurrence of constitutional chromosomal syndromes with high clinical significance in modern medical genetics are an important breakthrough. They contribute to a more comprehensive genetic delineation of past human populations and give impetus to perform more historic/prehistoric studies to discover other contemporary genetic disorders. A molecular profiling of ancient DNA (aDNA) from human remains added to anthropological and archaeological data may also give a broader picture of the social and historical contexts of individuals who were affected by genetic diseases. These advances in the detection of chromosome aneuploidies and previous discoveries of current monogenic syndromes in archaic hominins also highlight the possibility of detecting other genetic diseases of present-day occurrence in our ancestors. As a result, it might be feasible to delineate the evolutionary history of modern genetic diseases, establishing a timeline of their emergence, patterns of mutations, putative mechanisms of selection, and genomic mechanisms involved.

Objectives: Penile cancer, while relatively rare compared to other male malignancies, has seen an increased global incidence, with 36,068 new cases reported in 2020. This condition primarily affects regions with low human development indexes, notably India, China and Brazil. The mainstay of treatment is often partial or total penectomy, which has a profound impact on patients' emotional and social lives. Due to limited options for early diagnosis, non-surgical treatments, restricted healthcare funding and the negative consequences of mutilating surgeries, penile cancer is often considered a neglected disease. Penile cancer exhibits various histological types, but penile squamous cell carcinoma (SCC) is the most prevalent, accounting for 95% of cases worldwide. Multiple risk factors are associated with this condition, largely tied to lifestyle behaviors, such as promiscuous sexual behavior, zoophilia, poor hygiene, phototherapy, smoking and obesity. Human papillomavirus (HPV) infection is a significant etiological factor, particularly in squamous cell carcinomas. The prevalence of HPV in penile neoplasia varies widely, and its association with mortality remains uncertain.

Objectives: The Fanconi anemia (FA) genes are a family of at least 23 known genes that are spread across many chromosomes and participate in interstrand crosslink (ICLs) DNA repair. In this pathway, FA proteins are involved in sensing sites of ICLs, translocating repair enzymes from the cytoplasm to the nucleus, excising the area of damage, and facilitating repair of the fractured DNA. Mutations in these genes lead to Fanconi anemia, a syndrome characterized primarily by pancytopenia but with associated symptoms involving nearly every organ system; the majority of patients present with dermatological symptoms and growth deficits. Additionally, individuals with Fanconi anemia are known to be predisposed individuals to an increased risk of malignancies, particularly acute myeloid dystrophy and myelodysplastic syndrome, but also in the head, neck, esophagus, reproductive organs, brain, skin, liver, and kidneys. In fact, the cytogenetic aberrations seen in those with FA-associated AML differ from those in typical AML. In contrast, the cytogenetic changes seen in FA-associated MDS are similar to those in typical MDS.

Objectives: B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent cancer in United States children. In recent years, immunotherapies using chimeric antigen receptors (CAR T-cells) have improved prognosis for patients with B-ALL. Previous CAR T therapies have used CD19 as a target, but loss of this protein through antigen escape may cause relapse with slim chance of remission. For patients facing relapsed/refractory B-ALL, the need for new targets is evident. In this review, we focus on the KMT2A, IKZF1-related, and DUX4r subgroups of B-ALL, highlighting proven and potential CAR T targets. With a focus on genetics, we discuss chondroitin sulfate proteoglycan 4 as a target in mixed lineage rearranged leukemia and the use of proteomic analysis to locate other B-ALL antigenic surface markers, including the targeting of CD72 within a nanobody-based framework. Additionally, we examine the thymic stromal lymphopoietin receptor as a target in B-ALL with IKAROS family zinc finger 1 deletion across various subgroups. Following this, we propose the adaptation of CD371 as a CAR T-cell target for relapsed/refractory DUX4r B-ALL in the context of promising results from studies in acute myeloid leukemia. Finally, we provide a brief overview of other relevant therapies, including tyrosine kinase inhibitors and a planned universal CAR T for off-the-shelf use, before concluding with a case study that emphasizes the necessity of novel CAR T targets.