Journal of the Association of Genetic Technologists最新文献

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.

Objectives: Precursor B-cell acute lymphoblastic leukemia (B-ALL) is one of the most common neoplasms. It is characterized by genetic and epigenetic aberrations. The most remarkable mechanisms involved in epigenetic abnormalities are DNA methylation and acetylation. Methylation of CpG islands in promoter regions and acetylation of lysine residues regulate gene expression. Several studies have shown that patients with B-ALL show aberrant DNA methylation in a genome-wide scale. Histone deacetylases (HDAC) regulate gene expression by removing acetyl groups from lysine residues and histone acetyltransferase (HAT) adds acetyl groups. A hematologic malignancy like B-ALL may be very sensitive to small-molecule inhibitors that target these epigenetic mechanisms and therefore may induce expression of pro-apoptotic factors. Thus, HDAC inhibitors (HDACi), DNA methyltransferase inhibitors (DNMTi) and histone acetyltransferase inhibitors (HATi) have been developed as therapies. The objective of this review is to summarize the different epigenetic mechanisms involved in B-ALL.

Objectives: Turner syndrome was first described to encompass a shared set of physical features displayed by a subset of female patients including short stature and lack of sexual development. Half of cases are due to complete loss of an X chromosome, while the remainder are due to other alterations of the X chromosome that disrupt genes necessary for normal physical and sexual development. The SHOX gene, located at Xp22.33, is essential for the growth and maturation of bone, while genes on Xq are important for ovarian function. Thus, loss of an X chromosome results in phenotypic short stature and amenorrhea typically seen in Turner syndrome. We present a unique case of Turner syndrome in a 16-year-old girl with primary amenorrhea and above-average height, in which karyotype revealed a derivative X chromosome resulting in partial Xp trisomy and partial Xq monosomy [46,X,der(X)(pter->q21.2::p11.23->pter)]. We hypothesize this unique karyotype explains the atypical phenotypic presentation of this patient.

Objectives: Acute T-lymphoblastic leukemia (T-ALL) is a malignancy of immature T-cells in children and adults and although it occurs less frequently than B-ALL, it carries a worse prognosis, especially after relapse. Molecular characterization and subtyping of T-ALL has begun to reveal vital insights into the complex biology of T-ALL and has prognostic and therapeutic implications. We present a case of a 19-year-old male who was found to have an early cortical phenotype T-ALL with multiple cytogenetic and somatic mutations including t(10;14) TLX-1 translocation, 9p22 CDKN2A deletion and missense mutations in PHF6, NOTCH-1, and FBXW7. Characterization of the significance of these mutations reveals that PHF6 mutations occur more frequently in adult males in association with TLX-1 translocations and early cortical phenotypes with NOTCH-1 activating mutations. We show mechanistically that these alterations occur in concert with one another to drive cell growth, cell survival and cell cycle progression. While still in development, further characterization of T-ALL is essential to provide more prognostic and therapeutically useful information.

Objectives: Disorders of sex development (DSD) include a group of conditions in which genotypes do not correlate with the typical male and female phenotypes. Numerical and structural abnormalities involving both autosomes and sex chromosomes have been observed in DSD. Specifically, deletions, duplications, and translocations involving specific genes as well as point mutations and less common aberrations have been implicated in the pathogenesis of these conditions. Finally, recent advances in analytical tools, namely chromosomal microarrays and sequencing methods, have greatly enhanced the precision with which DSD are genetically characterized and phenotypically correlated. Herein we report a case of a 24-year-old female patient who presented with secondary amenorrhea. Cytogenetic studies of her peripheral blood showed an abnormal clone with 45,X in three cells and the other was initially observed by chromosome analysis as 46,X,+mar in 27 cells. Molecular cytogenetics were performed to characterize the marker chromosome that showed two copies of the SRY, two copies of the heterochromatin Yq12, and two copies of the Y centromere Yp11.1-q11.1 on the marker chromosome, resulting in the identification of an isodicentric Y chromosome. Females with a 46,XY karyotype have gonadal dysgenesis and typically present as mosaic, along with a 45,X cell line. Some show small deletions of the short arm of the Y chromosome. Further studies based on the clinical picture, as well as possible prophylactic gonadectomy due to an increased risk of gonadal malignancy, gonadoblastoma or dysgerminoma, are suggested. Genetic counseling was recommended.