Acute myeloid leukemia (AML) is a heterogeneous disorder characterized by a wide range of genetic defects. Cytogenetics, molecular and genomic technologies have proved to be helpful for deciphering the mutational landscape of AML and impacted clinical practice. Forty-eight new AML patients were investigated with an integrated approach, including classical and molecular cytogenetics, array-based comparative genomic hybridization and targeted next generation sequencing (NGS). Various genetic defects were identified in all the patients using our strategy. Targeted NGS revealed known pathogenic mutations as well as rare or unreported variants with deleterious predictions. The mutational screening of the normal karyotype (NK) group identified clinically relevant variants in 86.2% of the patients; in the abnormal cytogenetics group, the mutation detection rate was 87.5%. Overall, the highest mutation prevalence was observed for the NPM1 gene, followed by DNMT3A, FLT3 and NRAS. An unexpected co-occurrence of KMT2A translocation and DNMT3A-R882 was identified; alterations of these genes, which are involved in epigenetic regulation, are considered to be mutually exclusive. A microarray analysis detected CNVs in 25% of the NK AML patients. In patients with complex karyotypes, the microarray analysis made a significant contribution toward the accurate characterization of chromosomal defects. In summary, our results show that the integration of multiple investigative strategies increases the detection yield of genetic defects with potential clinical relevance.

Tumor growth and metastasis are reliant on intricate interactions between the host immune system and various counter-regulatory immune escape mechanisms employed by the tumor. Tumors can resist immune surveillance by modifying the expression of human leukocyte antigen (HLA) molecules, which results in the impaired presentation of tumor-associated antigens, subsequently evading detection and destruction by the immune system. The management of chronic lymphocytic leukemia (CLL) is based on symptom severity and includes various types of targeted therapies, including rituximab, obinutuzumab, ibrutinib, acalabrutinib, zanubrutinib, idelalisib, and venetoclax. These therapies rely on the recognition of specific peptides presented by HLAs on the surface of tumor cells by T cells, leading to an immune response. HLA class I molecules are found in most human cell types and interact with T-cell receptors (TCRs) to activate T cells, which play a vital role in inducing adaptive immune responses. However, tumor cells may evade T-cell attack by downregulating HLA expression, limiting the efficacy of HLA-dependent immunotherapy. The prognosis of CLL largely depends on the presence or absence of genetic abnormalities, such as del(17p), TP53 point mutations, and IGHV somatic hypermutation status. These oral targeted therapies alone or in combination with anti-CD20 antibodies have replaced chemoimmunotherapy as the primary treatment for CLL. In this review, we summarize the current clinical evidence on the impact of HLA- and cytokine-type responses on outcomes after targeted therapies currently used to treat CLL.

Summary Purpose The primary objective of this study was to evaluate the compliance of Romanian physicians with the national therapeutic protocol and international guidelines on treatment with erythropoiesis-stimulating agents in anemic cancer patients receiving chemotherapy. The secondary objective was to assess the hemoglobin (Hb) level change due to anemia treatment and safety of darbepoetin alfa. Methods This was a single-arm, prospective, longitudinal, multicenter, observational study in patients with nonmyeloid malignancies and symptomatic chemotherapy-induced anemia treated concomitantly with darbepoetin alfa. Patients were followed for the duration of chemotherapy, but no shorter than three and no longer than eight cycles, irrespective of their exposure to darbepoetin alfa. Results In this study, 497 patients with a mean age of 60.6 years were analyzed. Most patients (80.7%) were initiated on darbepoetin alfa at a Hb of 9–11 g/dL, congruent with recommendations. The median Hb increased by 0.9 g/dL between baseline and week 12. Hb target achievement was higher among patients treated according to guidelines than those initiated at Hb < 9 g/dL. A similar trend was observed for red blood cell transfusion requirements. No new safety signals were reported for darbepoetin alfa. Conclusions The majority of patients were treated according to national and international recommendations. Guideline adherence was associated with more frequent achievement of Hb targets and lower red blood cell transfusion requirements compared with patients starting anemia treatment with darbepoetin alfa at lower-than-recommended Hb levels.