Journal of the Association of Genetic Technologists最新文献

Objectives: B-cell acute lymphoblastic leukemia (B-ALL) is a subset of ALL that comprises 75% of ALL cases. There are a variety of chromosome aneuploidy or chromosomal rearrangements implicated in B-ALL. Deregulation of CRLF2 expression is seen in 5-15% of B-ALL patients and occurs primarily via a reciprocal translocation with immunoglobulin heavy chain (IGH), rearrangements of CRLF2, deletion within the PAR1 region of the X and Y chromosomes, and CRLF2 mutations as well as mutations of the CRLF2-involved pathways and are seen in Ph-like B-ALL. They are associated with a poor prognosis. Blinatumomab is an available immunotherapy, and there are currently a few ongoing clinical trials to treat CRLF2 B-ALL. This review focuses on the role of CRLF2 in B-ALL and summarizes the literature regarding its molecular pathways, clinical significance, incidence rates across demographics, therapies, and areas of further research.

Objectives: A recent report described a novel use of CMA for the first time in dogs that uncovered three cases of constitutional aneuploidy among 2,053 purebred and mixed-breed dogs. This advance is very significant because cytogenetic analysis by traditional methods in domestic dogs is technically difficult and may not conclusively identify all the abnormalities. This success with CMA testing anticipates the potential to discover more cases of canine aneuploidies as this technology becomes part of routine clinical genetic testing. As a whole, extended use of CMA is likely to uncover a wider range of chromosomal abnormalities that cause canine diseases, characterize in more detail the canine karyotype (normal and abnormal), and provide thorough cytogenomic data of an animal model useful to study human diseases. Since the platform developed for CMA that was used also allows mutation analysis for canine gene diseases, this additional technical feature permits a cost-effective and comprehensive genetic testing for diagnosis in only one step.

Objectives: Fluorescence in situ hybridization (FISH) is a quick and reliable test to detect the reciprocal t(15;17)(q22;q21) translocation in acute promyeloid leukemia (APL). The typical signal pattern for positive t(15;17) is one red, one green, and two fusion when using a PML/RARA dual fusion translocation probe. However, for variant translocations leading to the fusion of a RARA gene with an alternate gene partner, a RARA break-apart probe should be used to verify the RARA rearrangement. The typical signal pattern for a positive RARA break-apart probe is one red, one green, and one fusion. In this study, we report a rare APL case with a PRKAR1A-RARA fusion gene with a signal pattern distinct from that of t(15;17) and its other variants.

Objectives: A recent NGS study in patients with MDS demonstrated that molecular as well as cytogenetic abnormalities in cfDNA from peripheral blood mirror the profile in bone marrow. Such results give further support to a promising option of testing cfDNA to characterize and monitor MDS instead of using invasive bone marrow biopsies. This breakthrough expands the potential of cfDNA studies in hematologic disorders. It also suggests that the routine testing could incorporate cfDNA in the future once validation and standardization procedures are established and large clinical trials are completed.

Objectives: Noninvasive prenatal testing (NIPT) is a screening method used to detect the most common fetal aneuploidies using cell-free fetal DNA (cffDNA) obtained from maternal blood. Due to the high sensitivity and specificity, low false positive rate, and use as early as 10-weeks' gestation NIPT has been rapidly integrated into prenatal care. While NIPT is an excellent screening tool, the results can be influenced by many factors including placental mosaicism, maternal aneuploidy or mosaicism, and occult maternal malignancy. The diagnosis and treatment of malignancy during pregnancy present many challenges ranging from the use of imaging techniques to the delivery of optimal therapy, weighing the unique risks to both the mother and the fetus. We present a case of a 30-year-old woman diagnosed with Hodgkin lymphoma after NIPT and outline the challenges in diagnosis and treatment of malignancy occurring during pregnancy.

Objectives: T-cell prolymphocytic leukemia, or T-PLL, is an extremely rare and highly metastatic neoplasm characterized by proliferating mature T-cells and genetic aberrations that often involve chromosome 14. While T-PLL is commonly accompanied by a complex karyotype, there is little analysis on such cases in existing literature and thorough discussions of the less "characteristic" cytogenetic mutations are particularly lacking. We present a case study of a 68-year-old male T-PLL patient with marked leukocytosis and a history of T-cell lymphoproliferative disorder. Chromosomal analysis revealed a complex karyotype that included a translocation of both copies of chromosome 14, rearrangements on 9p and 5p, isochromosome 8, deletion 11q, and monosomy 17. Molecular cytogenetic analysis indicated a rearrangement of TRD (14q11.2), loss of the ATM and CDKN2A signals, and gains of the RELN, TES and MYC signals. Many of these mutations have strongly corresponded to poor prognoses in patients with T-PLL and other leukemias, especially when appearing concurrently. However, there are still profound knowledge gaps in our understanding of many genetic aberrations and the significance of marker chromosomes in the context of T-PLL. Considering the lack of consensus on the improvement of patient outcomes in the past two decades as well as the frequency of a complex karyotype in T-PLL, this case study highlights the critical need of continued research efforts in profiling complex cases to provide potential avenues for novel therapeutic targets for T-PLL patients.

Objectives: Acute myeloid leukemia (AML) is a heterogeneous malignancy of precursor myeloid cells. Identification and understanding of chromosomal abnormalities are key diagnostic and prognostic factors for patients with AML, as they play an important role in risk stratification algorithms. Hypodiploidy, a rare cytogenetic abnormality resulting in a karyotype with fewer than 46 chromosomes, is a rare finding in AML. It is often characterized by the involvement of chromosomes 5, 7, and/or 17, as well as the structural aberration t(8;21)(q22;q22), which is frequently accompanied by the clonal loss of a sex chromosome. Modal number (MN) has been shown to play a role in prognosis, with lower values associated with poorer survival. While hypodiploidy is frequently discussed within the context of acute lymphoblastic leukemia (ALL), its impact has garnered little relevance within AML studies. In this review, we aim to elucidate the characteristics of hypodiploidy in AML, investigate its prognostic significance, and explore its relationship with monosomal karyotypes, a more favored method of risk stratification.

Objectives: Acute myeloid leukemia (AML) is a clonal disorder of myeloid lineage precursors. Identification of cytogenetic aberrations is essential for classification and risk stratification of AML, with many demonstrating unique associations with various clinicopathologic features. One such abnormality is MYC amplification, a rare occurrence identified in less than 1% of AML patients. MYC is most commonly amplified in the form of double minutes, but may also occur via ring and marker chromosomes or homogeneously staining regions. Amplification of MYC often involves various chromosomal aberrations, including trisomies 4 and 6 and aneusomy of the sex chromosomes. In many cases, the presence of MYC amplicons is also associated with other negative prognostic factors, including complex karyotype and advanced age. Although MYC has been extensively investigated as a therapeutic target in various cancers, there are few studies examining the clinical significance of MYC amplification in AML. In this review, we explore recurrent cytogenetic abnormalities and demographic characteristics associated with amplification of MYC in patients with AML and discuss their diagnostic and therapeutic implications.

Objectives: Acute myeloid leukemia (AML) is a group of diseases resulting from a clonal expansion of myeloid precursor cells in the bone marrow. Each subtype harbors characteristic clinical, morphologic, and molecular features. AML is most often de novo and arises from somatic mutations causing unchecked proliferation of myeloblasts, but it may also present as a secondary malignancy, often as the result of prior cytotoxic exposure. Here we present a case of therapy-related AML (t-AML) following chemotherapy exposure found to have a characteristic balanced translocation involving 11q23 and outline a potential mechanism of oncogenesis.

Objectives: The FMS-like tyrosine kinase 3 gene (FLT3) is a receptor tyrosine kinase expressed in early hematopoietic progenitors that play an important role in hematopoietic development. The signaling pathways that are stimulated by the FLT3 protein manage several crucial cellular processes including division, growth, and survival of cells, specifically of hematopoietic progenitor cells. Activating mutations of this gene have been highly discussed in myeloid malignancies, including myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). However, FLT3 mutations are also observed in around 5% of acute lymphoblastic leukemia (ALL) patients. These mutations were usually found to be one of the four types: internal tandem duplications, tyrosine kinase domain mutations, juxtamembrane insertion and deletion, and juxtamembrane point mutation. The presence of FLT3 mutations in pediatric B-ALL patient populations tend to be associated with relapse and poor prognosis. These mutations are also correlated with poor prognosis in adult B-ALL patients. Due to the rarity of FLT3 mutations in B-ALL patients, there have been many challenges in attempts to understand their role in pathogenesis. In this review, we will discuss the most recent literature and trends associated with FLT3 mutations in B-ALL patients in order to elucidate their cytogenetic, molecular, and clinical implications.