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Summary Cytogenetics data, or karyotypes, are among the most common clinically used forms of genetic data. Karyotypes are stored as standardized text strings using the International System for Human Cytogenomic Nomenclature (ISCN). Historically, these data have not been used in large-scale computational analyses due to limitations in the ISCN text format and structure. Recently developed computational tools such as CytoGPS have enabled large-scale computational analyses of karyotypes. To further enable such analyses, we have now developed RCytoGPS, an R package that takes JSON files generated from CytoGPS.org and converts them into objects in R. This conversion facilitates the analysis and visualizations of karyotype data. In effect this tool streamlines the process of performing large-scale karyotype analyses, thus advancing the field of computational cytogenetic pathology. Availability and implementation Freely available at https://CRAN.R-project.org/package=RCytoGPS. The code for the underlying CytoGPS software can be found at https://github.com/i2-wustl/CytoGPS [ABSTRACT FROM AUTHOR]

Objectives: B-lymphoblastic leukemia (B-LBL) arising in patients with chronic lymphocytic leukemia (CLL) is exceedingly rare and poorly characterized. Methods: We describe four patients with CLL and concurrent or subsequent B-LBL diagnosed by morphologic, immunophenotypic, cytogenetic, and molecular analysis and reviewed the literature. Results: In three patients, B-LBL followed CLL by 5 to 15 years, and in one patient, B-LBL was diagnosed simultaneously with CLL. In all cases, the CLL had a typical immunophenotype, and the B-LBL blasts showed an immature B-cell immunophenotype with expression of CD10, CD19, and TdT and absence of surface immunoglobulin. In two patients, B-LBL blasts harbored t(9;22)(q34;q11.2)/BCR-ABL1. We sequenced the IGHV genes in both CLL and B-LBL in two patients and showed that IGHV usage differed. Conclusions: Our data suggest that at least some cases of B-LBL arising in patients with CLL are independent, secondary neoplasms rather than a manifestation of histologic transformation. [ABSTRACT FROM AUTHOR]

CD20 is an important therapeutic target in chronic lymphocytic leukaemia (CLL). In order to examine the relationship between CD20 expression and cytogenetic abnormalities, we correlated the fluorescent in-situ hybridization (FISH) genetic subtype of 510 treatment-naïve patients with CD20 expression as measured by quantitative flow cytometry. Patients were classified using the Dohner hierarchial classification. The median numbers of CD20 antigen sites by FISH subtypes were: 17p- ( n = 26), 9341 per cell; 11q- ( n = 42), 5886 per cell; +12 ( n = 93), 23 603 per cell; negative FISH ( n = 153), 8828 per cell; and 13q- ( n = 196), 10 781 per cell. Compared to cases with negative FISH, 11q- cases had significantly lower CD20 expression ( P = 0·001), and +12 cases had significantly higher CD20 expression ( P < 0·001). The significance of trisomy 12 and high CD20 expression was maintained after multivariate analysis accounting for other disease characteristics. Fifty-nine patients received the combination of rituximab and granulocyte-macrophage colony-stimulating factor as frontline therapy; responses were observed in 13 of 14 (93%) patients with +12, in two of four (50%) patients with 11q-, and in 30 of 41 (73%) patients with negative FISH, 13q- or 17p- CLL. Leukemic CD20 expression differed significantly between FISH subtypes. Patients with trisomy 12 CLL showed strong leukemic cell CD20 expression and had a high rate of response to rituximab-based therapy. [ABSTRACT FROM AUTHOR]

The t(14;19)(q32;q13), involving the BCL3 locus at chromosome 19q13 and the immunoglobulin heavy chain gene at 14q32, is a rare recurrent cytogenetic abnormality identified in B-cell neoplasms, most of which have been classified as chronic lymphocytic leukaemia (CLL) in the literature. We describe the clinicopathological, immunophenotypic and cytogenetic findings in seven patients with B-cell neoplasms associated with t(14;19)(q32;q13). There were five men and two women, with a median age of 48 years (range 33–68). All had absolute lymphocytosis, six had lymphadenopathy, and one had splenomegaly. Lymphocytes in blood and bone marrow aspirate smears were predominantly small and cytologically atypical. Flow cytometric immunophenotyping showed an atypical immunophenotype with low CLL scores. The growth pattern in bone marrow biopsy specimens was interstitial to diffuse; immunohistochemical stains were positive for bcl3 and negative for cyclin D1. Lymph node biopsy specimens of two patients revealed total architectural effacement by neoplasm with proliferation centres. In addition to t(14;19), cytogenetic studies demonstrated trisomy 12 in five patients. These results suggest that B-cell neoplasms with the t(14;19)(q32;q13) present frequently as leukaemia composed of small B-lymphocytes and share many features with CLL. However, these neoplasms also differ from CLL cytologically and in their immunophenotype. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented in which the editor discusses the clinical trial that integrates cytogenetic, next-generation sequencing (NGS), and laboratory data into prognostic analysis.

• Large-scale karyotype analysis of chronic myeloid leukemia (CML). • Novel method for analyzing text based (ISCN) karyotypes. • Demonstrated a proof of principle approach to identify disease subgroups based on cytogenetic profiling. • Determined 28 clusters from 4969 CML karyotypes based on cytogenetic profile. Karyotyping, the practice of visually examining and recording chromosomal abnormalities, is commonly used to diagnose diseases of genetic origin, including cancers. Karyotypes are recorded as text written in the International System for Human Cytogenetic Nomenclature (ISCN). Downstream analysis of karyotypes is conducted manually, due to the visual nature of analysis and the linguistic structure of the ISCN. The ISCN has not been computer-readable and, as such, prevents the full potential of these genomic data from being realized. In response, we developed CytoGPS, a platform to analyze large volumes of cytogenetic data using a Loss-Gain-Fusion model that converts the human-readable ISCN karyotypes into a machine-readable binary format. As proof of principle, we applied CytoGPS to cytogenetic data from the Mitelman Database of Chromosome Aberrations and Gene Fusions in Cancer, a National Cancer Institute hosted database of over 69,000 karyotypes of human cancers. Using the Jaccard coefficient to determine similarity between karyotypes structured as binary vectors, we were able to identify novel patterns from 4,968 Mitelman CML karyotypes, such as the co-occurrence of trisomy 19 and 21. The CytoGPS platform unlocks the potential for large-scale, comparative analysis of cytogenetic data. This methodological platform is freely available at CytoGPS.org. [ABSTRACT FROM AUTHOR]

Context.-Methods for plasma cell enrichment of bone marrow (BM) specimens can increase the sensitivity of fluorescence in situ hybridization (FISH) for detecting cytogenomic abnormalities. There are no published reports using these methods to evaluate high-risk cytogenomic abnormalities in patients with plasma cell neoplasms (PCNs) after therapy. Objective.-To evaluate the utility of plasma cell enrichment combined with FISH for detection of high-risk cytogenomic abnormalities in patients with PCNs after therapy. Design.-Twenty-eight patients with PCNs, of whom 22 received treatment, were included in this study. Plasma cells were enriched in BM aspirates by using a magnetic cell-sorting procedure to select CD138+ cells. Probes were chosen to assess for del(17p13/TP53), del(13q14/RB1), 1q21/CKS1B gain, IgH/FGFR3, and IgH/MAF. Clinicopathologic data were collected during clinical follow-up after plasma cell enrichment. Results.-Plasma cells in nonenriched BM specimens ranged from 1% to 28% (median, 8%) compared with 28% to 96% (median, 73%) in enriched BM specimens (P < .001). In a subset of treated patients in clinical remission, FISH detected high-risk cytogenomic abnormalities only in plasma cell-enriched samples. This approach also detected abnormalities in cases of solitary plasmacytoma and monoclonal gammopathy of undetermined significance. Conclusions.-Plasma cell enrichment of BM specimens increases FISH sensitivity for detecting high-risk cytogenomic abnormalities, particularly in treated patients, and these results, in combination with clinical follow-up data, can be of value to improve risk stratification and patient management. [ABSTRACT FROM AUTHOR]

Abstract: Deletions within the long arm of chromosome 15, a recurrent abnormality in myeloid malignancies, have been reported previously as a sole abnormality in only eight cases of acute myeloid leukemia (AML). We describe three new cases of AML with this abnormality, all adult women (age, 41–66 years). Two cases were acute myelomonocytic leukemia (FAB AML-M4), and one was acute myeloblastic leukemia with maturation (FAB AML-M2). The deletion was identified at initial diagnosis in one patient and at relapse in the other two. Although all received aggressive therapy, their survival was short. Taken together with the eight previously reported cases, we conclude that deletions in chromosome 15 are associated with AML, both in cases that arise de novo or in the setting of a myeloproliferative disorder or myelodysplastic syndrome. These cases often show features of myelomonocytic or monocytic differentiation. The prognosis is poor, with survival similar to other AML cases with unfavorable cytogenetic changes. [Copyright &y& Elsevier]