Journal of the Association of Genetic Technologists最新文献

Objectives: T-cell acute lymphoblastic leukemia (T-ALL) is a pervasive hematologic malignancy that arises from developmental and genetic abnormalities manifested in lymphoblasts belonging to the T-cell lineage. Responsible for 10-15% of pediatric acute lymphoblastic leukemia (ALL) and 25% of adult ALL patients, T-ALL is characterized not only by cytomorphic features, but also by the aberrant expression of specific genes critical to T-cell development. Such changes in the genome ultimately result in mutational and developmental cascades that alter the chromosomal constitution, the process of which are used to organize T-ALL cases into different subgroups according to specific gene expression signatures. Clinically, comprehensive categorizations are important in risk stratification, assessment, and treatment protocols. Notable genetic subgroups include that of TAL, TLX1, TLX3, HOXA, MYB, ETP and NKX2. Current research also recognizes phenotypic and immunologic categories, such as ALK-positive ALCL, ALK-negative ALCL, BIA ALCL, AITL, and PTCL, NOS, which has revolutionized our understanding of T-cell lymphoma. Furthermore, it has been suggested that most T-ALL patients present with abnormal NOTCH1 genes in addition to mutations involving the JAK-STAT signaling pathway. These abnormalities are associated with the regulatory malfunction of T-cell development as well as that of their respective tumor suppressors and oncogenes. While recent studies have revealed characteristic defects in T-ALL, the interactions between oncogenes and their tumor suppressors with leukemia development are not well known as the signaling pathways involved behind each genetic lesion have yet to be fully explored. Studies involving FISH, RT-PCR, aCGH, and NGS offer novel perspectives to potentially learn more about the pathogenesis and cytogenetics of T-ALL, a field that demands further attention and research.

Objectives: Acute myeloid leukemia (AML) is caused by the arrested differentiation and dysregulated proliferation of myeloid precursors. Many AMLs harbor genetic abnormalities which determine the molecular mechanisms of the disease and are associated with distinct clinical and pathological features, prognosis, and targeted therapies. We present a case of acute myeloid leukemia with t(6;9)(p23;q34.1) and review the classic clinical presentations and underlying pathogenesis of the disease.

Objectives: Acute myeloid leukemia (AML) with t(8;16)(p11.2;p13.3)/KAT6A-CREBBP is an uncommon subtype of AML accounting for less than 0.5% of AML cases. AML with t(8;16)/KAT6A-CREBBP has characteristic clinical and pathologic features including disseminated intravascular coagulation (DIC), leukemia cutis, hemophagocytosis, monocytic or myelomonocytic differentiation, is frequently associated with therapy-related AML and has a poor prognosis. We present a classic case of AML with t(8;16)/KAT6A-CREBBP occurring in a patient with both a germline NF1 mutation and recent cytotoxic therapy for embryonal rhabdomyosarcoma.

Objectives: Lymphoplasmacytic lymphoma (LPL, previously termed lymphoplasmacytoid lymphoma) is an uncommon mature B-cell lymphoma usually involving the bone marrow and less commonly the spleen and/or lymph nodes. The majority of patients with LPL have a circulating monoclonal immunoglobulin M (IgM) that can lead to a hyperviscosity syndrome known as Waldenström macroglobulinemia (WM). Although LPL appears to be a sporadic disease in the majority of cases, a familial predisposition is present in some cases. The main chromosomal abnormalities are trisomy 12, trisomy 3, isochromosome 6p, and 14q rearrangements involving IgH among complex karyotypes. Herein, we present an 89-year-old male patient who presents with LPL involving 80% of the marrow cellularity with circulating lymphoma cells. Chromosomal analysis detected two unrelated abnormal clonal populations: one clone has trisomy 12 as the sole abnormality in the stimulated culture, while the other clone has a 13q deletion as the sole abnormality in the cells from the non-stimulated culture. Trisomy 12 is one of the most common abnormalities in B-CLL and it is associated with an intermediate prognosis. Deletions 13q have been identified in B-cell malignancies, non-Hodgkin's lymphomas (NHL), as well as myelodysplastic syndromes and chronic myeloproliferative neoplasms (Heim and Mitelman, 2015). Trisomy 12/13q- FISH slide was reviewed looking at the segmented cells. Fifty segmented cells were scored and a 13q- pattern was detected in 36% (18/50) of the cells suggesting that this finding (the 13q- clone) may be myeloid in origin. Clinicopathologic correlation of these results was recommended.

Objectives: A 61-year-old male patient whose core needle biopsies of tissue involved a malignant lymphoid infiltrate composed of intermediate to large cells positive for CD20, PAX5, CD10, BCL6, BCL2, and cMYC, and negative for MUM1. Mitotic activity was brisk with a correspondingly high index of proliferation by Ki67 (~95%) and the patient was diagnosed with a diffuse large B-cell lymphoma, germinal center phenotype. DNA FISH analysis was performed on the paraffin embedded tissue from the right external iliac lymph node using the LSI BCL6 (3q27) and MYC (8q24) dual color break apart probes from Cytocell and the LSI BCL2 (18q21) dual color break apart probe from Abbott. We found rearrangements of BCL6 in 95% of the cells examined, MYC rearrangements in 77% of the cells and BCL2 rearrangements in 95% of the nuclei. These findings allowed us to classify this case as a triple-hit lymphoma now called "high-grade B-cell lymphomas" with MYC, BCL2, and/or BCL6 rearrangements.

Objectives: Interphase fluorescence in situ hybridization (FISH) cutoff values are calculated using various mathematical methods to determine whether abnormalities seen are at reportable (statistically significant) levels. However, for interphase FISH studies of samples obtained from oncology patients who have been transplanted or treated, these cutoff values may result in reporting a false negative result due to the small percentage of residual disease that falls below such a cutoff value. Failure to detect the rare abnormal cells may impact patient care and prognosis. For such situations, the two questions are: is the disease still present, and if so, how prevalent is it? The first question is qualitative and the second is quantitative. Traditionally, only the quantitative parameters have been used for determining reportability. Here we propose a method to account for both qualitative and quantitative evaluations of interphase FISH results.

Objectives: Interphase fluorescence in situ hybridization (FISH) cutoff values are calculated using various mathematical methods to determine whether abnormalities seen are at reportable (statistically significant) levels. However, for interphase FISH studies of samples obtained from oncology patients who have been transplanted or treated, these cutoff values may result in reporting a false negative result due to the small percentage of residual disease that falls below such a cutoff value. Failure to detect the rare abnormal cells may impact patient care and prognosis. For such situations, the two questions are: is the disease still present, and if so, how prevalent is it? The first question is qualitative and the second is quantitative. Traditionally, only the quantitative parameters have been used for determining reportability. Here we propose a method to account for both qualitative and quantitative evaluations of interphase FISH results.

Objectives: Diffuse large B-cell lymphoma (DLBCL) is a non-Hodgkin's lymphoma (NHL) that is the most common and the most aggressive or fast-growing form of NHL. It can lead to death if left untreated. Cytogenetic abnormalities include rearrangements of the IgH and BCL2 genes. Herein we described a t(8;14;22)(q24;q32;q11.2) within the context of a complex karyotype involving MYC/IGH/IGL in a three-way translocation that was characterized by molecular cytogenetics. The t(8;14)(q24;q32) is a recurrent chromosome abnormality described in non-Hodgkin lymphomas (NHL), especially in 80% of Burkitt lymphoma (BL) and diffuse large B-cell lymphomas. The variant t(8;22) (q24;q11) is also seen in these cases. MYC rearrangements have been observed in up to 10% of cases of diffuse large B-cell lymphomas (DLBCL) and is usually associated with a complex pattern of genetic alterations. This particular pattern with IGH-MYC rearrangements within the context of complex karyotypes is seen in diffuse large B-cell lymphomas. Complex karyotypes are associated with genomic instability and a poor prognosis.

Objectives: The use of imatinib has brought a standard shift in the management of chronic myeloid leukemia (CML) during the last two decades. In India, imatinib has been available for more than fifteen years and has been made available all over the country due to patient assistance programs and cheaper generic versions. Despite improvements in survival of CML patients, there are unique challenges in the Indian context. Indian patients present with more advanced disease. Most centers have access to imatinib as first-line therapy, but there is limited availability of molecular monitoring and second-line therapy. Most of the outcome data is retrospective and comparable with that reported in Western centers. Drug adherence is impaired in at least one third of patients and contributes to poor survival. The aim of this review is to highlight the fact that prospective studies and cooperative studies are very much needed to improve the quality of data available on Indian CML patients.

Objectives: We report the case of a 69-year-old male with peripheral blood findings of persistent anemia, mild absolute monocytosis with mild dysgranulopoiesis, rare circulating blasts, and mild thrombocytopenia. Bone marrow biopsy revealed hypercellular bone marrow (60%) with 3.4% blasts and mild dysgranulopoiesis, morphologically characteristic of myelodysplastic/myeloproliferative neoplasm, chronic myelomonocytic leukemia-1 (CMML-1). Chromosome analysis revealed an abnormal karyotype with an apparent monosomy 7 and the presence of one marker chromosome. FISH analysis of metaphases from destained G-banded slides revealed translocation of D7S486 to a derivative chromosome 21, and two copies of RUNX1 located on an isoderivative chromosome 7. This karyotype was then reinterpreted as an abnormal male karyotype with rearrangements of chromosomes 7 and 21 [ider(7)(q10)t(7;21)(q11.2;q11.2), der(21)t(7;21)], resulting in loss of 7p and gain of 21q, in 19 of the 20 metaphase cells examined. The remaining one metaphase was cytogenetically normal. Extra copies of RUNX1 and abnormalities of chromosome 7 are seen in myeloid disorders including MDS/MPN. Complex rearrangements such as the ones present in this study suggest genomic instability, which is usually associated with a poor prognosis.