Journal of the Association of Genetic Technologists最新文献

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.

Objectives: Up to 90% of cases of chronic myeloid leukemia (CML) are myeloproliferative disorders characterized by a Philadelphia (Ph) chromosome with a classical t(9;22)(q34;q11). Of all CML patients, 5-10% show variant Philadelphia translocations (vPh) and are an area of research interest for their significance in predicting response to various therapies, including tyrosine kinase inhibitors. They are also being studied for prognosticating multi-year survival outcomes in varied patient populations, with conflicting results. We included 238 patients for conventional cytogenetic and fluorescence in situ hybridization study from January 2018 to October 2018. Patients with vPh in CML-Chronic Phase (CML-CP) were analyzed with respect to their demographic parameters, response to imatinib therapy, and survival. Out of 238 patients diagnosed with CML-CP, 8 patients (3.3%) showed vPh. The most common chromosomes involved in these translocations were 1, 2, 3, 4, 7, 11 and 12. In almost all the cases with variant Ph chromosome, the BCR-ABL rearrangement was detected by molecular methods or by fluorescence in situ hybridization (FISH). All patients were treated with imatinib as a first-line therapy. Rates of complete hematological response, complete cytogenetic response, and major molecular response were similar in all patients with classical Ph and variant Ph chromosome. Our data suggest that prognosis of CML patients with vPh in CML has no significant effect in predicting response to imatinib or in predicting survival.

Objectives: We present the case of an 83-year-old female with a long history of B-CLL followed by observation only. Twelve years after her diagnosis of CLL, routine follow-up chromosome analysis of peripheral blood revealed an abnormal metaphase with a dup(3)(q21q27) in 18 of 20 metaphase cells. To further characterize the abnormal chromosome 3, fluorescence in situ hybridization (FISH) was performed using the Abbott BCL6 probe for 3q27. An additional BCL6 signal was observed in 303 of the 500 interphase nuclei examined. The ISCN was reported as 46,XX,dup(3)(q21q27)[1]/46,XX[2]. nuc ish(5'BCL6, 3'BCL6)x3(5'BCL6 with 3'BCL6x3)[303/500]. This abnormality was seen again in one of three available metaphases in a follow-up peripheral blood study five years later, consistent with persistent disease. Molecular genetic analysis identified the presence of somatic hypermutation of the immunoglobulin heavy chain gene variable region (IGH-V), which is recognized as an independent favorable prognostic marker in CLL. FISH analysis was negative for loss of SEC63 (6q21), amplification of MYC (8q24), loss of ATM (11q22.3), trisomy 12, loss of D13S319 (13q14.3), loss of TP53 (17p13.1) and CCND1/MYEOV IGH rearrangement [t(11;14)(q13;q32.30)]. Partial trisomy 3 is a relatively rare event seen in B-CLL, with commonly overrepresented segments including the q21-23 region and the q25-29 region of the long arm of chromosome 3, as well as changes leading to gains of 3q26- q27. The clinical significance of this finding in B-CLL is uncertain; however, our patient remains well and has not required therapy 17 years after her initial diagnosis.

Objectives: Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) accounts for ~15% of patients with high-risk ALL with an activated tyrosine kinase profile similar to Philadelphia chromosome positive ALL, without the presence of BCR-ABL1 rearrangement. ABL-class genes (ABL1, ABL2, PDGFRB, CSF1R and CRLF2) comprise the second major subgroup of Ph-like ALL cases but presence of ABL2 gene rearrangement in leukemia is rarely reported. We report a novel case of ABL2 chromosomal rearrangement that results from t(1;7)(q25;q32) in a patient with high-risk ALL.