Evolutionary Tracks of Chromosomal Diversification in Surgeonfishes (Acanthuridae: Acanthurus) Along the World’s Biogeographic Domains

Fishes of the genus Acanthurus (Acanthuridae) are strongly related to reef environments, in a broad biogeographic context worldwide. Although their biological aspects are well known, cytogenetic information related to this genus remains incipient. In this study, Acanthurus species from populations inhabiting coastal regions of the Southwest Atlantic (SWA), South Atlantic oceanic islands (Fernando de Noronha Archipelago and Trindade Island), Greater Caribbean (GC), and Indo-Pacific Ocean (the center of the origin of the group) were analyzed to investigate their evolutionary differentiation. For this purpose, we employed conventional cytogenetic procedures and fluorescence in situ hybridization of 18S rDNA, 5S rDNA, and H3 and H2B-H2A histone sequences. The Atlantic species (A. coeruleus, A. chirurgus, and A. bahianus) did not show variations among them, despite their vast continental and insular distribution. In contrast, A. coeruleus from SWA and GC diverged from each other in the number of 18S rDNA sites, a condition likely associated with the barrier created by the outflows of the Amazonas/Orinoco rivers. The geminate species A. tractus had a cytogenetic profile similar to that of A. bahianus. However, the chromosomal macrostructures and the distribution of rDNA and hisDNA sequences revealed moderate to higher rates of diversification when Acanthurus species from recently colonized areas (Atlantic Ocean) were compared to A. triostegus, a representative species from the Indian Ocean. Our cytogenetic data covered all Acanthurus species from the Western Atlantic, tracked phylogenetic diversification throughout the dispersive process of the genus, and highlighted the probable diversifying role of ocean barriers in this process.

Should We Look beyond Revised International Prognostic Scoring System: A Retrospective Observational Study of Progression of Myelodysplastic Syndrome to Acute Leukemia

Introduction Myelodysplastic syndrome (MDS) is a clonal stem cell disorder and heterogeneous condition resulting in peripheral cytopenias with marrow dysplasia due to ineffective hematopoiesis. The revised International Prognostic Scoring System (IPSS-R) predicts the risk of progression to acute leukemia (AL). Indian data on MDS and its progression to AL are limited. Additionally, the cytogenetic findings are dictated by patients' racial background. Study intended to analyze the cytogenetic profile of the patients with MDS. Objectives This study aimed to (1) evaluate the clinicohematologic and morphologic spectrum of newly diagnosed MDS cases, (2) evaluate the cytogenetic profile of these cases, and (3) study the cases progressed to AL. Materials and Methods MDS cases diagnosed and followed-up during a 5-year study period, from January 2015 to December 2019, were included in the study and the study was conducted at regional cancer center in Western India. De novo diagnosed MDS cases with complete workup were considered and MDS due to secondary causes were excluded. Baseline clinical, hematologic findings were tabulated along with cytogenetics and risk stratified as per IPSS-R, and their progression was studied. Results A total of 63 cases of de novo MDS were diagnosed over a period of 5 years with 45 cases on follow-up and 15 cases (33.3%) progressed to AL. Maximum number of cases belonged to MDS-excess blast (EB) category accounting to 48 cases (76.1%). Apparently normal karyotyping was the commonest cytogenetic finding in 33 MDS cases (61.2%) and in 8 cases that progressed to AL (53.4%). Conclusion MDS cases diagnosed at relatively early age were at higher risk of progression to AL. Majority of the cases that progressed to AL were risk stratified in high and very high risk groups and 10 cases which progressed to AL belonged to good category, interestingly apparent normal karyotyping was the commonest cytogenetic finding in more than 50% of the cases progressed to AL. Molecular mutations could only explain this progression and studies integrating molecular mutations with present IPSS-R scoring system should be conducted, as it could translate into better risk stratification and help in early identification and better management of cases at risk in progression to AL.

Therapy-Related Myeloid Neoplasms in 109 Patients Following Radiation Monotherapy

Therapy-related myeloid neoplasms (t-MNs) are a late complication of cytotoxic therapy and are defined as a distinct entity by the World Health Organization. While the link between chemotherapy exposure and risk of subsequent t-MN is well-described, the association between radiation monotherapy (RT) and t-MN risk is less definitive. We analyzed 109 consecutive patients who developed t-MNs after RT and describe latencies, cytogenetic profile, mutation analyses, and clinical outcomes. The most common cytogenetic abnormality was a clonal abnormality in chromosome 5 and/or 7, which was present in 45% of patients. The median latency from RT to t-MN diagnosis was 6.5 years, with the shortest latency in patients with balanced translocations. 1-year overall survival (OS) was 52% and 5-year OS was 22% for the entire cohort. Patients with chromosome 5 and/or 7 abnormalities experienced worse 1-year OS (37%) and 5-year OS (2%) when compared to other cytogenetic groups (p<0.0001). 16 patients underwent NGS; ASXL1 and TET2 were the most commonly mutated genes (n=4). In addition, 17 patients underwent germline variant testing and 3 carried pathogenic or likely pathogenic germline variants. In conclusion, patients with t-MN after RT monotherapy have increased frequencies of chromosome 5 and/or 7 abnormalities, which are associated with poor overall survival. In addition, pathogenic germline variants may be common in patients with t-MN after RT monotherapy.

Cytogenetic evaluation of α, β-amirina obtained in resin of Protium heptaphylum (Aubl.) Marchand in polychromatics erythrocytes of mice swiss.

The Amazon Rainforest has a great variety of medicinal plants, among them we can highlight the “Almecegueira” or “Breu Branco” (Protium heptaphylum) in Portuguese, the producer of a greenish-white resin that hardens when it touches the air, known by its gastroprotective and anti-inflammatory effects. These effects are attributed to a triterpene mixture of α and β amirine, predominant in the resin. The purpose of the study is to obtain a cytogenetic profile to the α, β-amirine mixture obtained in the resin of P. heptaphylum. For this, the micronucleus test was used in peripheral blood and bone marrow; administering solution in Swiss mice with the dosages of 1mg/Kg, 3mg/Kg, and 10mg/Kg, diluted in 5% DMSO, the effects were observed in 24h and 48h after the treatment. For the test in peripheral blood the mice’s caudal vein was punctured, while for the bone marrow test, the femurs of the animals were obtained from which bone marrow samples were taken. It was found that in peripheral blood, the administration of the compounds did not cause genotoxicity in 24h and 48h, in contrast, antigenotoxicity was, for concentrations 1; 3 and 10mg/kg, respectively 10%; 12%; 67% in 24h and 9%; 15%; 73% in 48h. In the bone marrow, no genotoxicity was observed, as for antigenotoxicity was observed that for concentrations 1; 3 e 10mg/kg the percentage of reduction was respectively: 11%, 15%, and 30% in 24h and 13% 16% 33% in 48h. It is concluded that the studied compound can be an alternative for treatments in the future since it presents low toxicity and high antigenotoxic potential.

Myeloid neoplasms in the setting of chronic lymphocytic leukaemia/chronic lymphocytic leukaemia-like disease: a clinicopathological study of 66 cases comparing cases with prior history of treatment to those without

AimsMyeloid neoplasms occur in the setting of chronic lymphocytic leukaemia (CLL)/CLL-like disease. The underlying pathogenesis has not been elucidated.MethodsRetrospectively analysed 66 cases of myeloid neoplasms in patients with CLL/CLL-like disease.ResultsOf these, 33 patients (group 1) had received treatment for CLL/CLL-like disease, while the other 33 patients (group 2) had either concurrent diagnoses or untreated CLL/CLL-like disease before identifying myeloid neoplasms. The two categories had distinct features in clinical presentation, spectrum of myeloid neoplasm, morphology, cytogenetic profile and clinical outcome. Compared with group 2, group 1 demonstrated a younger age at the diagnosis of myeloid neoplasm (median, 65 vs 71 years), a higher fraction of myelodysplastic syndrome (64% vs 36%; OR: 3.1; p<0.05), a higher rate of adverse unbalanced cytogenetic abnormalities, including complex changes, −5/5q- and/or −7/7q- (83% vs 28%; OR: 13.1; p<0.001) and a shorter overall survival (median, 12 vs 44 months; p<0.05).ConclusionsMyeloid neoplasm in the setting of CLL/CLL-like disease can be divided into two categories, one with prior treatment for CLL/CLL-like disease and the other without. CLL-type treatment may accelerate myeloid leukaemogenesis. The risk is estimated to be 13-fold higher in patients with treatment than those without. The causative agent could be attributed to fludarabine in combination with alkylators, based on the latency of myeloid leukaemogenesis and the cytogenetic profile.

Cytogenetic Changes in Multiple Myeloma Timeline: A Tertiary Center's Experience

Introduction Risk stratification in Multiple Myeloma according to cytogenetic abnormalities has been utilized clinically to guide understanding of prognosis. Specific cytogenetics abnormalities such as deletion 17p, t(14,16) and t(4,14) have been associated with more aggressive disease and poor outcome[1]. It has been postulated that genetic aberrations evolve in a temporal pattern in non-hyperploid multiple myeloma such that 13q deletion and t14q32 tend to be early events while chromosome 1 and 17 abnormalities occur as later events [2]. Furthermore, other studies have suggested higher frequencies of high risk cytogenetic abnormalities (such as deletion 17p and gain of 1q) at relapse after upfront autologous stem cell transplant [3]. Our study examined the cytogenetic profile of patients treated at a tertiary health system at the time of diagnosis and at first relapse, irrespective of bone marrow transplant and treatment Methods This is a retrospective study of patients treated at Henry Ford Cancer Institute/Henry Ford Health System. Subjects were adults diagnosed with multiple myeloma with relapse confirmed by a bone marrow biopsy between January 2014 and January 2019. The cytogenetic profile at time of diagnosis and relapse for each patient was reviewed. Exclusion criteria included history or current diagnosis of another malignancy. 145 cases were identified, of which 112 cases were excluded: 19 cases with plasmacytoma but no bone marrow relapse, 32 with other malignancy, 21 with relapse before study period, 5 with relapse after study period, and 35 with bone marrow biopsy or cytogenetics not available for review. As such, we analyzed the remaining 33 cases Results 26 of the 33 cases underwent a bone marrow transplant. A third of the patients (11) developed new mutations, which included 17p deletion (3), 13q deletion (1), chromosome 1 abnormality (1), new trisomies (5), t(11,14) (4), hypoploidy (1), and IgH/CCDN1 changes (1). Conclusion Though cytogenetic evolution in multiple myeloma has been studied, not all patients undergo a bone marrow biopsy and cytogenetic evaluation at relapse, which limits this assessment. Despite our sample size being limited as a majority of the study population did not have cytogenetics recorded at relapse, our study reveals that new mutations can arise in a significant proportion of patients at relapse, some of which are known to be associated with poor prognosis. This can be potentially prognostic, as presence of new high-risk mutations could alter the presumed disease trajectory, and these could also have therapeutic consequences. While further studies with a larger sample size are needed to determine the frequencies of each mutation, our study underscores the importance of dedicated monitoring of cytogenetics at each relapse in multiple myeloma. References Palumbo, A., et al., Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol, 2015. 33(26): p. 2863-9. Jimenez-Zepeda, V.H., E. Braggio, and R. Fonseca, Dissecting karyotypic patterns in non-hyperdiploid multiple myeloma: an overview on the karyotypic evolution. Clin Lymphoma Myeloma Leuk, 2013. 13(5): p. 552-8. Merz, M., et al., Longitudinal fluorescence. Haematologica, 2017. 102(8): p. 1432-1438. Disclosures No relevant conflicts of interest to declare.