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Differential gene expression analysis by suppression subtractive hybridization with correlation to the metabolic pathways involved in chronic myeloid leukemia (CML) may provide a new insight into the pathogenesis of CML. Among the overexpressed genes found in CML at diagnosis are SEPT5, RUNX1, MIER1, KPNA6 and FLT3, while PAN3, TOB1 and ITCH were decreased when compared to healthy volunteers. Some genes were identified and involved in CML for the first time, including TOB1, which showed a low expression in patients with CML during tyrosine kinase inhibitor treatment with no complete cytogenetic response. In agreement, reduced expression of TOB1 was also observed in resistant patients with CML compared to responsive patients. This might be related to the deregulation of apoptosis and the signaling pathway leading to resistance. Most of the identified genes were related to the regulation of nuclear factor κB (NF-κB), AKT, interferon and interleukin-4 (IL-4) in healthy cells. The results of this study combined with literature data show specific gene pathways that might be explored as markers to assess the evolution and prognosis of CML as well as identify new therapeutic targets. [ABSTRACT FROM AUTHOR]

Dasatinib has demonstrated efficacy in patients with chronic-phase chronic myeloid leukemia (CML) who had resistance or intolerance to imatinib. However, some patients also develop resistance or intolerance to dasatinib. To identify potential molecular pathways involved in primary resistance to dasatinib in CML, we analyzed gene expression profiles of mononuclear cells of 7 imatinib-resistant patients, collected before and after 1-year dasatinib treatment. Large-scale gene expression was measured with Agilent microarrays covering protein-coding genes and long (>200 nt) noncoding RNAs (lncRNAs). Sets of genes and lncRNAs significantly differentially expressed (>1.5 fold-change; q value ≤10%) were identified. Ingenuity Pathway Analysis pointed to a number of functions, canonical pathways and gene networks that were significantly enriched with differentially expressed genes. In addition to protein-coding genes, lncRNAs have been recently implicated in pathways leading to tumorigenesis. Our data point to new possible regulatory elements involved in dasatinib resistance in CML. [ABSTRACT FROM AUTHOR]

Male gender was recently reported as an adverse prognostic factor in patients with diffuse large B-cell lymphoma (DLBCL) treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). We conducted a retrospective study of adult patients with DLBCL initially treated with rituximab containing regimens between 2001 and 2007. Patients were identified from the clinical archives of 43 Italian and Brazilian institutions. The principal endpoint was overall survival (OS). One thousand seven hundred and ninety-three patients were fully eligible for the study. Thirty-eight percent, 27%, 22% and 12% of patients had an International Prognostic Index (IPI) score of 0-1, 2, 3 and 4-5, respectively; 53% were males. After a median follow-up of 36 months (1-106), the 5-year OS was 76% (95% confidence interval 74-78%). In univariate analysis, male gender was an adverse prognostic factor with a hazard ratio of 1.52. In multivariate analysis, when adjusted by IPI, again gender maintained its prognostic relevance, showing an independent additive effect. In conclusion, in patients with DLBCL treated with rituximab containing regimens, gender may increase the predictive power of the IPI. Based on these results, given possible differences in blood clearance of rituximab between males and females, the benefit of higher doses of rituximab in males should be explored. [ABSTRACT FROM AUTHOR]

Neoplastic cells in classical Hodgkin's lymphomas (cHL) seem to correspond to defective germinal center B-cells, which escape from apoptosis. Epstein-Barr virus (EBV) may be implicated in this protective mechanism. The aim of the present study was to determine the expression of apoptosis-related proteins in cHL among adult patients and correlate them with EBV expression, clinical findings and survival. EBV was detected by in situ hybridization (Epstein-Barr Encoded RNA, EBER, probe). Immunohistochemistry was used on paraffin sections to detect LMP-1/EBV, CD15 and the apoptosis-related proteins (bcl-2, bax, bcl-X, mcl-1 and CD95). Seventy-eight patients seen at our Institution were studied: 36 male and 42 female. Median age was 31 years (15-75 years). Histological types of cHL were: 61 nodular sclerosis (47 NS1 and 14 NS2), 15 mixed cellularity (MC), 1 lymphocyte depletion and 1 unclassified. In 50 cases there was EBV expression (64%). At least one apoptosis-associated protein was expressed in 92% and CD15 in 57.7% of the cases. In the univariate analysis, the following variables were related to a better overall survival: expression of CD15 (p = 0:023), expression of mcl-1 protein (p = 0:029), expression of bcl-2 protein (p = 0:028, only in a Cox model after stratification for histology) and expression of LMP-1 (p = 0:042). EBV expression presented a borderline inverse correlation with bcl-2. A prognostic index (PI) developed in the present study revealed that simultaneous expression of bcl-2, mcl-1 and LMP-1 was significant and independently correlated with an excellent survival. [ABSTRACT FROM AUTHOR]

AbstractThis study investigates COVID-19 outcomes and immune response in chronic myeloid leukemia (CML) patients post-SARS-CoV-2 vaccination, comparing effectiveness of various vaccine options. Data from 118 CML patients (85 in Brazil, 33 in the US) showed similar infection rates prior (14% Brazil, 9.1% US) and post-vaccination (24.7% vs. 27.3%, respectively). In Brazil, AstraZeneca and CoronaVac were the most commonly used vaccine brands, while in the US, Moderna and Pfizer-BioNTech vaccines dominated. Despite lower seroconversion in the Brazilian cohort, all five vaccine brands analyzed prevented severe COVID-19. Patients who received mRNA and recombinant viral vector vaccines (HR: 2.20; 95%CI 1.07–4.51; p < .031) and those that had achieved at least major molecular response (HR: 1.51; 95% CI 1.01–3.31; p < .0001) showed higher seroconversion rates. Our findings suggest that CML patients can generate antibody responses regardless of the vaccine brand, thereby mitigating severe COVID-19. This effect is more pronounced in patients with well-controlled disease. [ABSTRACT FROM AUTHOR]

This is the largest Latin American study of BCR-ABL mutations in chronic myeloid leukemia (CML) patients, resistant to imatinib (IM). In 195/467 (41%) patients, mutations were detected. The most frequent mutation was T315I (n = 31, 16%). Progression-free (PFS) and overall survival (OS) at 5 years were lower in patients with BCR-ABL mutations (43% vs. 65%, p = 0.07 and 47% vs. 72%, p = 0.03, respectively) and in those with the T315I mutation (p = 0.003 and p = 0.03). OS and PFS were superior in subgroup who switched to second generation inhibitors (SGIs) after IM failure (OS: 50% vs. 39% p = 0.01; PFS: 48% vs. 30% p = 0.02). BCR-ABL mutations conferred a significant poor prognosis in CML patients. [ABSTRACT FROM AUTHOR]