Journal of the Association of Genetic Technologists最新文献

Objectives: Noonan syndrome (NS) is a relatively common autosomal dominant disorder with characteristic features and molecular alterations. The most common recurrent alteration is in the PTPN11 gene, a proto-oncogene that encodes a cytoplasmic receptor tyrosine phosphatase and helps regulate kinase activity and control cell survival and replication. Mutations in this gene can increase the risk for the development of multiple different malignancies, particularly hematopoietic. Here we present a case of NS with a PTPN11 mutation demonstrating the classic presentation of Noonan syndrome as well as the expected clinical follow-up.

Objectives: We report a 74-year-old male whose bone marrow morphology, flow cytometry, MRI and serum electrophoresis showed evidence of plasma cell myeloma. Chromosome analysis of the bone marrow showed an abnormal karyotype, described as 51~53,XY,+3,+5,t(8;14)(q24 .1;q32),+9,+11,+15,+19,+21[cp6]/46,XY[14]. The t(8;14)(q24.1;q32) is mainly seen in Burkitt lymphoma but it can also be seen in plasma cell myeloma usually with the context of a complex karyotype. Based on the Mitelman database the involvement of C-MYC is usually seen in late tumor progression in plasma cell myeloma as a secondary rearrangement, usually during clonal evolution and divergence and is associated with a significantly decreased survival. Our case pinpoints the involvement of MYC abnormalities in plasma cell myeloma as well as the importance of cytogenetics as a tool to manage and monitor plasma cell myeloma cases.

Objectives: We report on a rare case of B-cell prolymphocytic leukemia (B-PLL) in a patient with a history of chronic lymphocytic leukemia (CLL) that showed a novel translocation t(10;22)(q21;q11.22) and an interstitial deletion of 11q14.1-q23.3 in 2017. The chromosome microarray analysis (CMA) confirmed the 11q22 deletion and revealed a small interstitial deletion of IGL gene. In 2018, the patient presented with worsening lymphocytosis, anemia and thrombocytopenia. The peripheral blood smear revealed an increased prolymphocyte population, which comprised 60.4% of lymphoid cells, establishing a diagnosis of B-cell prolymphocytic leukemia. The CMA and G-banded chromosome analysis showed one additional aberration in the form of 1q gain translocated onto the other homologue 22. These findings suggested clonal evolution of CLL to B-PLL. The most common translocation involving immunoglobulin lambda chain (IGL) in CLL is the t(18;22), followed by t(8;22) and (11;22). An evolution to B-PLL occurs in most cases without gaining additional aberrations. Here, we report for the first time a novel translocation involving IGL with chromosome 10q21 and one 1q gain occurring in a patient with CLL that transformed to B-PLL. Based on the disease progression and this newly developed cytogenetic aberration, our case supports the progressive nature of CLL in the presence of IGL deletion and suggests the pathological role of 1q gain in CLL transformation.

Objectives: Myelodysplastic syndromes present with a range of cytogenetic abnormalities that are used to guide diagnosis and management of the disease. Herein, we present the case of a 72-year-old female patient who presented with pancytopenia. Peripheral blood showed Hb 9.0 g/dl, neutrophils less than 1800/mm3, and platelets less than 100,000/mm3. Bone marrow showed erythroid hyperplasia, megaloblastic changes, dyserythropoiesis, multinuclearity, nuclear bridges, nuclear budding, atypical mitoses, and ring sideroblasts. Also, CD34 and CD117 as well as myeloperoxidase positive populations were present. On this basis, a diagnosis of myelodysplastic syndrome was rendered. Chromosome studies showed an abnormal female karyotype with an isochromosome 17q as well as deletion 20q in 17 of the 20 metaphase cells examined. The remaining three cells were cytogenetically normal. Molecular cytogenetic studies using a TP53-specific probe showed only one TP53 signal in 87% of the nuclei examined. An i(17q) as a sole cytogenetic aberration is rare among both MDS and myeloid malignancies in general, but is functionally similar to aberrations of 17p that lead to loss of TP53. This case provides further insight into the spectrum of cytogenetic abnormalities present in MDS.

Objectives: Whole-arm translocations are relatively rare among hematological malignancies. There are a few reports on der(18;21)(q10;q10). This is a recurrent but rare abnormality. Only about 11 cases harboring der(18;21)(q10;q10) have been reported. However, combined der(18;21) (q10;q10) and gain of chromosome 21 is even rarer, with only three cases reported. The previous cases were with AML, AML-M2, and aCML diagnosis. We report the first case of Ph-like, B-lymphoblastic leukemia (B-ALL) with +21 and der(18;21)(q10;q10) which resulted in loss of 18p and a gain of 21q. We address tumorigenesis and morphological characteristics of hematological malignancies involving der(18;21)(q10;q10), along with a review of the literature.

Objectives: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological disease caused by genetic abnormalities that manifest during the development of T-cell precursors, encompassing 15% of pediatric and 25% of adult ALL cases. While T-ALL and its heterogeneous genomic landscape has been well-characterized by establishing different subtypes and risk stratification for patients, the expression and activity of microRNAs (miRNAs) in T-ALL have not been investigated as extensively as cytogenetic and genomic abnormalities. miRNAs are prospective biomarkers that can be critical in improving diagnostic measures for T-ALL, expanding risk categorizations of patients for select therapies, and as target candidates for interventional treatments. Certain miRNAs have been found to be dysregulated as a result of mechanisms underlying T-ALL pathophysiology, including aberrant signaling pathways and epigenetics. Through the implementation of more robust bioinformatics such as miRNA target prediction tools, next-generation sequencing, and standard molecular techniques, recent research has underscored the significant contribution of miRNAs toward the development and progression of T-ALL by altering canonical signaling pathways associated with T-ALL such as NOTCH1, mTOR, and PI3K/AKT. In this review, we summarize the recent findings surrounding the expression and activity of dysregulated miRNAs and how they contribute to the onset and course of disease in T-ALL. As dysregulated miRNAs have been shown to elicit positive and negative responses, the dual effects of miRNAs demand additional research to elucidate miRNAs for target treatments in addition to profiling T-ALL further as a malignant disease.

Objectives: Introduction: The BCR-ABL fusion gene plays a central role in the pathogenesis of CML. The aim of the present study was to evaluate BCR-ABL fusion gene expression in CML patients and to correlate with clinical outcome. Method: A total of 112 CML patients were enrolled for the current study and expression of the BCR-ABL fusion gene was performed using qRT-PCR. Statistical analysis of SPSS correlated the BCR-ABL gene copy number and ratio with distinct parameters. Result: We observed that BCR-ABL gene CN and ratio were significantly higher in adult CML patients as compared to childhood leukemia (p=0.02 and p=0.04, respectively). BCR-ABL CN and ratio were significantly increased in CML patients with leukocytosis (p=0.01 and p=0.008, respectively) and thrombocytosis (p=0.05 and p=0.008, respectively). Further, CN and ratio were compared with three prognostic scores; Sokal, Hasford and EUTOS score. BCR-ABL CN and ratio were higher in high risk category for Sokal and EUTOS (European Treatment and Outcome Study) scores. Conclusion: The current study strengthens clinical importance molecular response and prognosis of CML patients.

Objectives: Transient myeloproliferative disorder (TMD), now more commonly known as transient abnormal myelopoiesis (TAM), is a condition closely associated with Down syndrome. Ninety-five percent of Down syndrome cases occur as a result of chromosomal nondisjunction and are rarely due to mosaicism or translocation. TMD is found exclusively in neonates and is most commonly characterized by trisomy 21, somatic GATA1 mutation, and the increased presence of megakaryoblasts. TMD often does not manifest clinically, but patients may show hepatomegaly, splenomegaly and other symptoms. While TMD is almost always present with trisomy 21, there are not many other cytogenetic abnormalities associated with TMD, with a few rare cases such as monosomy 7 and trisomy 8. Recent studies have suggested liver hematopoietic progenitor cells as the candidate for TMD origin. Furthermore, GATA1 mutations associated with TMD are found to encode for a stop codon in the N-terminal activation region of gene sequences. It has been shown that those mutations can cause overproliferation of megakaryocytes, which can cooperate with Down syndrome cells, which have trisomy 21, in the progression of TMD into acute megakaryoblastic leukemia (AMKL). Since GATA1 mutations are present in all cases of myeloid leukemia of Down Syndrome, monitoring GATA1 in patients with trisomy 21 may assist with earlier diagnosis of TMD. Another likely cause of TMD is the amplification of the RUNX1 transcription factor gene located on chromosome 21. It has been shown that RUNX1 is associated with leukemias of myeloid lineage. While most cases of TMD will spontaneously resolve, some will evolve into acute myeloid leukemia (AML). In this review, we will discuss the cytogenetic, molecular genetics and clinical aspects of TMD.

Objectives: Blastic plasmacytoid dendritic cell neoplasm (BPDCN), previously known as natural killer (NK) cell leukemia/lymphoma, is categorized by the World Health Organization as a sole entity. Most often, BPDCN presents with features of both lymphoma and leukemia. The average age at diagnosis is 60 to 70 years and there are more men than women who are diagnosed with BPDCN. Herein we report a 67-year-old female with a recent peripheral blood morphology revealing a hematopoietic leukemia process. Flow cytometry revealed an atypical cell population without B-cell or T-cell lineage expression. It was positive for CD45 and CD123 and negative for CD34. The peripheral blood showed blastic plasmacytoid dendritic cell neoplasm, macrocytic anemia and moderate thrombocytopenia. Chromosome analysis showed an abnormal clone with i(7)(q10) and monosomies of chromosomes 13 and 15. She underwent a bone marrow biopsy. Bone marrow and peripheral blood showed a blastic plasmacytoid dendritic cell neoplasm (BPDCN), hypercellular marrow (estimated 95%) with 90.4% blasts (aspirate smear).

Objectives: Chronic lymphocytic leukemia (CLL) is among the most common forms of leukemia diagnosed in the United States. It is associated with a variety of clinically significant genetic abnormalities, including cytogenetic abnormalities that are assessed routinely. Herein, we present a case of CLL for which molecular cytogenetic analysis revealed concomitant deletion of TP53 (17p13.1) in 87% of cells analyzed and amplification (3-20 signals) of C-MYC (8q24.1) in 47% of cells analyzed. Although rearrangements involving C-MYC are common in CLL, amplification is a rarer phenomenon that has not been investigated as thoroughly and may be overlooked during routine analysis. We review this case in the context of available literature on the plethora of genetic abnormalities involving C-MYC in CLL and their relevance to the pathogenesis of the disease. All in all, this case highlights the role of comprehensive, multidisciplinary genetic testing in the management of CLL.