Journal of the Association of Genetic Technologists最新文献

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.

Objectives: Recent NGS studies in multiple myeloma identified in one step and with comparable high accuracy to the concurrent cytogenomic tests the characteristic IGH translocations and copy number abnormalities. In addition, NGS allowed detection of gene mutations. This unprecedented success of a comprehensive genomic analysis suggests the possibility of replacing the separate tests in current use (cytogenetics, FISH, SNPs microarray and mutation analysis) with a single more efficient NGS assay. Down the road, NGS appears to have the potential to improve routine patient care with the clinical application of a detailed genomic profile.

Objectives: We present the case of a 56-year-old male with myelodysplastic syndrome (MDS) whose bone marrow immunophenotype showed lower positivity for CD45 and positivity for CD34; 8.66% of this population also expressed partial positives for MPO, CD16, CD117, CD36, CD33, and CD71, as well as positives for CD13, HLA-DR, and CD11b. No alterations in the pattern of maturation were seen in CD13 vs CD16 and CD13 vs CD11b. An analysis of a population of mature lymphocytes revealed CD45 high CD3+ in 87.5% of cells, CD45 high CD19+ in 7.6% of cells, and 4.9% NK cells. These results are consistent with a myelodysplastic syndrome with an excess of blasts type 1. Chromosome analysis of the bone marrow revealed an abnormal karyotype with a t(1;6)(p12;p11.1) as well as deletion 5q and a ring 11 in 12 of the 20 metaphase cells examined. The t(1;6)(p12;p11.1) has not been reported in association with any particular hematological malignancy and provides further insight into the range of cytogenetic abnormalities in MDS.

Objectives: B-Acute lymphoblastic leukemia (B-ALL) is a malignant disease that arises from several cooperative genetic mutations in a single B-lymphoid progenitor, leading to altered blast cell proliferation, survival and maturation, and eventually the lethal accumulation of leukemic cells. B-ALL accounts for about 12% of all childhood and adult leukemias diagnosed in developed countries, and 60% of those diagnosed are patients younger than 20 years old. As the most common cancer in children (25% of all cases) with a peak incidence in patients between the ages of two and five years, with a second, smaller peak in the elderly, the factors predisposing children and adults to ALL remain largely unknown. Herein we present an eight-year-old male patient diagnosed with B-ALL. Chromosome studies of 20 G-banded metaphases of the bone marrow detected an abnormal male karyotype with loss of 9p [i(9)(q10)] and loss of 17p [der(17)(?::17q11.2->17p11.2::17p11.2->17qter)] within the context of a complex karyotype in eight metaphase cells. Four of these abnormal metaphases showed additional material of unknown origin on chromosome 12 at p11.2 [add(12)(p11.2)]. Metaphase FISH analysis was crucial to characterize such complex chromosomal abnormalities, underscoring the importance of molecular cytogenetics in characterizing complex karyotypes in this hematological malignancy.

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.