Journal of the Association of Genetic Technologists最新文献

Objectives: A 75-year-old male presented with back pain, abdominal discomfort, and weight loss, and was subsequently found to have a pancreatic head mass. Biopsy confirmed diffuse large B-cell lymphoma (DLBCL), and the patient achieved radiographic remission with chemotherapy. However, fluorescence in situ hybridization (FISH) analysis unexpectedly revealed Philadelphia chromosome-positive (Ph+) cells in the bone marrow and peripheral blood, establishing concurrent chronic myeloid leukemia (CML). Despite targeted therapy for CML, at last follow-up, the patient still has detectable BCR::ABL1. This rare case highlights the diagnostic importance of comprehensive staging and cytogenetic testing, as well as the therapeutic challenge of managing synchronous lymphoid and myeloid neoplasms.

Objectives: Chromosome translocations involving the RUNX1 gene at 21q22 are recurring abnormalities in acute myeloid leukemia (AML). t(8;21)(q22;q22) is the most common translocation involving the RUNX1 gene, which is categorized as an independent type of acute leukemia in the WHO classification system. The translocation results in a frame fusion of RUNX1::RUNX1T1, which is considered to be the pathogenesis of neoplasm development. The present report describes an AML case displaying a t(8;21)(q22;q22)-like translocation by initial chromosome analysis, but subsequent FISH analysis did not show the fusion signals corresponding to the RUNX1::RUNX1T1 fusion gene. Reverse transcriptase polymerase chain reaction (RT-PCR) also failed to identify the formation of the RUNX1::RUNX1T1 fusion gene. Reassessment of chromosome analysis in light of the FISH and RT-PCR data yielded a t(8;21) (q23;q22) translocation.

Objectives: Acute myeloid leukemia (AML) is a blood cancer characterized by the overproduction of myeloid precursors within the bone marrow, resulting in disrupted hematopoiesis. Chromosomal abnormalities provide valuable insights into the development of AML and serve as key indicators of patient outcomes and treatment strategies. Numerous genetic abnormalities can be seen in AML. Here, we describe a case of a 34-year-old patient with AML-M5. Biopsy and immunophenotyping confirmed AML-M5, while conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis revealed trisomy of chromosomes 7 and 12, and an isochromosome (i)(Xq10). Trisomies of such chromosomes and i(Xq10) in combination are rare and carry different prognostic significance. In this case, the patient died within three days of diagnosis, demonstrating a poor prognosis. Hence, identification of such numerical chromosomal abnormalities in AML-M5 can help in patient stratification, tailored medicine, and risk assessment.

Objectives: This case report presents the findings of a genetic analysis using conventional cytogenetics and fluorescence in situ hybridization (FISH) to investigate a chromosomal abnormality in a patient with developmental delay and dysmorphic features. The patient was diagnosed with a 48,XY,t(6;11)(q27;q23) translocation and tetrasomy 21. Chromosomal analysis is essential for the diagnosis and risk stratification of all leukemia patients. Not surprisingly, racial differences in chromosomal aberrations (CA) in hematological malignancies could be found, and CA incidence in leukemia might change over time, possibly due to environmental and lifestyle changes. The t(6;11)(q27;q23) translocation is a significant chromosomal rearrangement linked to acute leukemia, particularly acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). This translocation disrupts normal hematopoietic processes by fusing the KMT2A (MLL) gene on 11q23, a master regulator of gene transcription with the MLLT4 (AF6) gene on 6q27, leading to oncogenic transformation and aggressive disease progression. Conventional cytogenetic analysis revealed the presence of an additional chromosome 21 and a translocation between chromosomes 6 and 11, which were further confirmed by FISH. This case highlights the significance of cytogenetic techniques in identifying complex chromosomal disorders and provides insights into the clinical implications of such abnormalities.

Objectives: Chronic myeloid leukemia (CML) is typically characterized by the presence of the BCR-ABL1 fusion gene on chomosome 22 resulting from a t(9;22)(q34;q11.2) translocation. We report a case of a 59-year-old female with CML in the chronic phase, initially presenting with thrombocytosis and diagnosed with t(9;22) via conventional karyotyping and fluorescence in situ hybridization (FISH). Nine years and seven months after the initial diagnosis, despite treatment with standard imatinib mesylate therapy (400 mg daily), conventional cytogenetic analysis revealed the emergence of trisomy 8 and a pericentric inversion of chromosome 16 (inv(16) (p13q22)) in cells that already carried the t(9;22). Bone marrow aspiration and biopsy showed 80% blasts, predominantly expressing myeloid markers CD13, CD33, CD117, along with HLA-DR and CD34. Both FISH and conventional karyotyping confirmed the presence of trisomy 8, inversion of chromosome 16, and t(9;22). Additionally, reverse transcription-polymerase chain reaction (RT-PCR) confirmed the presence of the BCR-ABL fusion gene. The coexistence of these genetic abnormalities is often associated with an aggressive clinical course, rapid disease progression, and chemotherapy resistance. Following disease progression, the patient was treated with a combination of hydroxyurea (500 mg) and decitabine (50 mg), and her tyrosine kinase inhibitor (TKI) therapy was switched to bosutinib (400 mg). Despite these interventions, she developed pleural effusions and lung metastases and ultimately passed away approximately seven months after initiating the new treatment due to relapsed disease and infectious complications.

Objectives: We report the case of a 50-year-old male with acute myeloid leukemia (AML). Chromosome analysis revealed an abnormal karyotype with a t(6;20)(q13;q11.2) and a complex rearrangement leading to an extra derivative chromosome 1 [der(1)(14q32->14p13::1p13->1q44] which was confirmed by metaphase FISH. FISH analysis confirmed an extra copy of 1q25 in 30.5% [61/200] of the nuclei examined. Rearrangements leading to an extra copy of 1q are common in AML, but translocations involving chromosomes 6 and 20 are rarely observed. Both were seen previously in this patient, suggesting persistence of this patient's neoplasm. Only six cases in the literature describe translocations between chromosomes 6 and 20. However, the breakpoints found in our patient [t(6;20)(q13;q11.2)] appear to be unique. Further studies need to be conducted to determine if this is a common/rare abnormality in AML. Also, there was a complex rearrangement involving chromosomes 1 and 14, which was characterized by metaphase FISH, which is still a powerful tool for detecting complex rearrangements in the clinical cytogenetics laboratory.

Objectives: A recent prospective study run by the IDENTIFY project at the U.S. National Institutes of Health (NIH) uncovered occult cancers in pregnant or postpartum women who previously received Non-Invasive Prenatal Testing (NIPT) reports of atypical abnormal/ unreportable results that were discordant with the fetal genotype. Among 107/117 patients enrolled who received a full evaluation, 52 (48.6%) had cancers, mostly lymphomas (31/52), colorectal tumors (9/52), and breast cancer (4/52). These results were gathered through standardized research cfDNA sequencing in peripheral blood and a comprehensive cancer screening protocol. Most of these patients (47/52) showed a sequencing pattern in cfDNA of multiple subchromosomal and/or whole gains and losses in multiple chromosomes (≥3). This pattern was interpreted as a high-risk indicator of cancers. Except for whole-body MRI imaging, which was very effective in discovering tumors (49/101 cases), the rest of the cancer screening was not informative. The whole data strengthen the view that NIPT has clinical value for a preliminary identification of pregnant women who may have hidden malignancies and should be referred for a thorough cancer screening. In addition, a uniform follow-up protocol of comprehensive cancer screening allowed the diagnosis of a substantial number of cancers that otherwise would not have been detected. Overall, these results from IDENTIFY, the first via a prospective study, also represent progress in guidelines for improved identification and management of occult malignancies coexisting with pregnancies.

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.