The impact of increasing karyotypic complexity and evolution on survival in CLL patients treated with ibrutinib.

Complex karyotype defined as ≥3 cytogenetic abnormalities is prognostic of survival in patients treated with ibrutinib or venetoclax in relapsed/refractory (RR) chronic lymphocytic leukemia (CLL). Recent studies re-evaluating this dichotomous variable have shown that higher numbers of cytogenetic abnormalities (i.e. ≥5) have a worse overall survival in patients treated with chemoimmunotherapy. We sought to determine if increasing karyotypic complexity, treated as a continuous variable, was prognostic of survival for patients treated with ibrutinib for CLL. We conducted a retrospective analysis of all patients with CLL treated with single-agent ibrutinib or in combination with an anti-CD20 antibody at our institution. We included 456 patients with both treatment-naïve (TN) and RR disease. Median number of prior therapies was 2 (range 0-13), 30% of patients had del(17p), and 75% were IGHV unmutated. 50% had ≥3 cytogenetic abnormalities including 30% with ≥5. In a multivariable analysis, increasing karyotypic complexity was an independent predictor of shorter progression-free survival (HR 1.07 (95% CI 1.04-1.10), p<0.0001) and overall survival (HR 1.09 (95% CI 1.05-1.12), p<0.0001). Furthermore, we found that presence of clonal evolution determined by cytogenetic analysis at progression was prognostic of subsequent survival (p=0.02). This solidifies karyotypic complexity as an important prognostic factor for CLL patients treated with ibrutinib. Further research should consider sequential karyotypic analysis as a determination of risk of progression and death in patients with CLL.

Molecular analysis reveals high diversity in the Hoplias malabaricus (Characiformes, Erythrinidae) species complex from different Amazonian localities

ABSTRACT DNA barcoding proposes that a fragment of DNA can be used to identify species. In fish, a fragment of cytochrome oxidase subunit I (COI) has been effective in many studies with different foci. Here we use this molecular tool to provide new insights into the cryptic diversity found in the Hoplias malabaricus species complex. Popularly known as trahira, H. malabaricus is widely distributed in South America. The clade shows molecular and cytogenetic diversity, and several studies have supported the occurrence of a complex of species. We performed molecular and karyotypic analysis of H. malabaricus individuals from eight Amazonian localities to assess the diversity present in the nominal taxon, and to clarify relationships within this group. We used 12 samples in cytogenetic analyses and found two karyomorphs: 2n = 40 (20m + 20sm) (karyomorph C) and 2n = 42 (22m + 20sm) (karyomorph A). We used 19 samples in molecular analyses with COI as a molecular marker, maximum likelihood analyses, and the Kimura-2-parameter evolutionary model with bootstrap support. We found karyomorph-related differentiation with bootstrap of 100%. However, we found high molecular diversity within karyomorph C. The observed pattern allowed us to infer the presence of cryptic diversity, reinforcing the existence of a species complex.

Cytogenetic analysis reveals the swamp status of the indigenous “Bhangor” buffalo population from Tripura state

The domestic water buffalo (Bubalus bubalis) are classified into the swamp and riverine. However, their hybrids are also found in some parts of Assam (Brahmaputra Valley) in North-east India. Swamp buffaloes have a typical phenotypic appearance, like the shape of horns, small size, and body-color, etc. This study characterizes the indigenous ‘Bhangor’ buffalo population from the Tripura state using cytogenetic analyses. The blood of buffaloes samples were collected across the state, phenotypically identified as swamp buffaloes were cultured, terminated, and harvested using conventional karyotype protocol to determine the number of chromosomes. We have characterized ‘Bhangor’ an indigenous buffalo population from Tripura state using karyotypic analysis for the first time to confirm that all animals phenotypically identified as swamp buffaloes with 2N=48 chromosomes.

Chromosomal instability in different species of agricultural animals (review)

The purpose of the work was to analyze the frequency of chromosomal instability in different species of agricultural animals in Western Siberia on the basis of literature data. The analysis of the literature on the topic of somatic chromosomal instability in agricultural animals has been carried out. Despite the stability of the chromosome set, deviations from it are quite common. It is noteworthy that chromosomal instability is characteristic of almost all individuals in the population and serves as an important indicator for assessing the natural mutability of chromosomes. It has been found if an aberration appeared in one tissue, it is very likely to occur in others. It has been noted that somatic chromosomal instability occurs in animals with reduced reproductive function, as well as those suffering from any pathology. For example, in calves with parakeratosis the increase in the frequency of chromatid and isochromatid breaks has been found. Analysis of the frequency of aberrations in sires, which differ in the level of perinatal mortality of offspring revealed the increased percentage of offspring mortality in fathers with the large number of chromosomal disorders. Therefore, low fertilization, spontaneous abortions and stillbirths may be indications for karyotypic analysis. It has been revealed that the lability of the karyotype is inherent in all animal species, regardless of the species, sex and age, as well as the morphofunctional state. The data on some types of somatic chromosomal instability in different types of farm animals in Western Siberia has been presented. Such indicators as the frequency of polyploidy, the number of cells with fragments of chromosomes, as well as single and paired fragments of chromosomes has been given. Different types of chromosomal instability varied depending on the animal species and climate zone. The presented data can be accepted as a physiological norm and used in veterinary medicine and animal science.

The First Karyological Analysis of the Sixbar Grouper Epinephelus sexfasciatus (Valenciennes, 1828) (Perciformes, Epinephelinae)

This study examines for the first time of karyotypic analysis and chromosomal characteristic of nucleolar organizer regions/NORs of Epinephelus sexfasciatus. The fish samples were collected from Andaman Sea, Phuket province, southern Thailand. The chromosomes were investigated using conventional Giemsa’s staining and Ag-NORs banding techniques. Fish chromosome preparations were conducted by squash technique from kidney. The results showed that the diploid chromosome number of E. sexfasciatus was 2n=48 and the fundamental number (NF, number of chromosome arms) was 48. The type of chromosomes included 24 large telocentric and 24 medium telocentric chromosomes. After Ag-NOR banding technique, single pair of NORs was observed on the short arm of medium telocentric chromosome pair 23. The idiogram shows gradually decreasing length of the chromosomes. A size difference of the largest and the smallest chromosomes is approximately two folds. The karyotype formula could be infered as: 2n(48) = 2n(48)= Lt24+Mt24.

Non Random Distribution of Chromosome-21 in Syndromic Cases of Wilms’ Tumors

Wilms’ tumors are the common embryonic childhood solid tumor of kindney and heterogeneous in nature. Karyotypic analysis of Wilms’ tumor has shown a variety of chromosomal aberrations with different (%) frequency of structural and numerical changes in somatic cell. Present study were carried out in eleven cases (n=11) of Wilms’ tumors with different age group (betwen 1.5 year to 10 year). Most striking feature is the involvement of high frequency (>60%) of Wilms’ tumor shows extra copy of chromosome-21 in the karyotypes after using high resolution of GTG banding and FISH analysis. Interestingly, 18% cases of Wilms’ tumor shows loss of Y-chromosome and appearance of (r)Y reporting first time in India. Beside this, short arm of chromosome - 6 and 16 shows two new break points i.e. 6q21.22 and 16q23 might have play an significant role in Wilms’ tumors progression. The other relevant findings were the association of either gain (trisomy) or loss (monosomy) of chromosome with chromatid break points, ring, dicentric or rearrangements of chromosome (translocation) with different frequency. However, this is a rare coincidence that environmental factor (s) might have increase risk of developing Down syndrome (47,XY+21) in Wilms’ tumors, due non - disjunction event and unequal crossing over in cell- division of the disease outcome.

Chemical composition, antimicrobial activity and chromosome number of Hertia cheirifolia L. from Algeria

The aims of this work are to investigate the chemical composition, the antibacterial activity of the essential oil and the chromosome numbers of two populations of Hertia cheirifolia. The samples were collected in the flowering stage, in eastern Algeria locality. The aerial parts of H. cheirifolia were submitted to a hydro-distillation. GC and GC / MS analysed the chemical compositions of the obtained essential oils. The antibacterial activity of essential oils was evaluated using the disks diffusion method against ten bacterial strains. For karyotypic analysis, the squashing method is used. Fifty-eight compounds representing 98.93% of the total oil were identified in H. cheirifolia. The chemical composition is dominated by the presence of major products, α-pinene (48.49 - 53.85%) and Germacrene-D (2.64 - 12.66%). Two distinct chemical breeds were identified, the α-pinene-spathulenol of Batna population, and the α-pinene-germacrene-D of Setif population. The essential oil of H. cheirifolia has a moderate activity against bacteria tested. In contrast, the strains E. coli ATCC 25922, P. syringae ATCC 53543 and E. fecalis ATCC 49452 are resistant to H. cheirifolia essential oils. The observations of root cells meristematic at metaphase of H. cheirifolia gave a diploid chromosome number 2n = 2x = 20, with a basic chromosome number (x= 10).

SPECIES SPECIFICITY OF HETEROCHROMATIN BLOCK DISTRIBUTION AND rDNA LOCALIZATION IN MITOTIC CHROMOSOMES OF MOSQUITOES SPECIES AEDES EXCRUCIANS, AE. BEHNINGI AND AE. PUNCTOR

A karyotypic analysis of three mosquito species Aedes excrucians, Ae. behningi and Ae. punctor (Diptera: Culicidae). Differences in the lengths of chromosomes, the distribution of C- and DAPI blocks of heterochromatin, and the localization of rDNA genes on chromosomes were revealed. Aedes excrucians has the largest chromosome length among the three species represented. Ae. punctor differs in the localization of rDNA on the second chromosome, while in Aedes excrucians and Ae. behningi, rDNA genes are located on chromosome 1. All three species have different C-banding and species-specific localization of heterochromatin DAPI blocks. Consequently, chromosome analysis can serve as an additional mechanism for species identification of mosquitoes of the genus Aedes.

A Case of 14-Year-Old Male with Fibroma of Tendon Sheath of the Hand with Novel Chromosomal Translocation 4;10

Fibroma of tendon sheath (FTS) is an uncommonly encountered soft tissue mass, which is morphologically distinct from the more commonly seen giant cell tumor of tendon sheath (GCTTS). Initially described in 1936, FTS is typically a slow growing, painless, firm mass with a predilection for the upper extremity, frequently involving the hand. Cases of associated triggering or compression neuropathies have been described when underlying tendons or nerves are affected. Currently, the literature on FTS is sparse and largely limited to case reports. More recently, few reports of cytogenetic analysis on FTS have been reported in the literature. Cellular and chromosomal analysis of FTS tissue revealed chromosomal translocations with yet unknown clinical significance. Here, we present a case report of FTS in a 14-year-old male with a painless enlarging mass on the palmar side of the left hand treated by excision. Subsequent karyotypic analysis revealed a chromosomal translocation t(4;10) (p16;q24), add (10)(q22)[24]. To our knowledge, this is the first description of this chromosomal aberration in the literature.