Nanocapsules provide selective delivery and increase the bioavailability of bioactive compounds. In this study, we examined the anticancer and immunomodulatory potential of Fridericia chica (crajiru) extract encapsulated in nanocapsules targeting myeloid leukemias. Nanocapsules containing crajiru (nanocapsules-CRJ) were prepared via interfacial polymer deposition and solvent displacement. Size and polydispersity were measured by dynamic light scattering. Biological assays were performed on leukemia cell lines HL60 and K562 and on non-cancerous Vero cells and human PBMC. The anticancer activity was evaluated using cytotoxicity and clonogenic assays, while the immunomodulatory activity was evaluated by measuring the levels of pro- and anti-inflammatory cytokines in PBMC supernatants treated with concentrations of nanocapsules-CRJ. Nanocapsules-CRJ exhibited significant cytotoxic activity against HL60 and K562 cells at concentrations ranging from 0.75 to 50 μg/mL, with the greatest reductions in cell viability observed at 50 μg/mL (p < 0.001 for HL60; p < 0.01 for K562), while not affecting non-cancerous Vero cells and human PBMCs. At concentrations of 25 μg/mL and 50 μg/mL, nanocapsules-CRJ reduced the formation of HL60 and K562 colonies by more than 90% (p < 0.0001). Additionally, at a concentration of 12 μg/mL, nanocapsules-CRJ induced the production of the cytokines IL-6 (p = 0.0002), IL-10 (p = 0.0005), IL-12 (p = 0.001), and TNF-α (p = 0.005), indicating their immunomodulatory potential. These findings suggest that nanocapsules-CRJ hold promise as a potential therapeutic agent with both cytotoxic and immunomodulatory properties.

Myeloid sarcoma (MS) is a very rare disease in both adults and children. Prognosis is poor in adults; in the pediatric age, the prognostic impact of extramedullary disease is controversial. Systemic therapy represents the mainstay of treatment even in isolated MS, but a comparison between different induction regimens is very limited in the literature. To date, it is still not clear if induction treatment should differ from that of other acute myeloid leukemias and stem cell transplant is considered for consolidation in both leukemic patients and in those with isolated disease. Our study describes a retrospective series of 13 cases of MS (adults and children), diagnosed and treated at our institute over 18 years. We report the results of immunophenotypic, cytogenetic and molecular studies, therapeutic approaches, and outcome, in order to establish the best strategy for patients\' workup.

Amino acid (AA) metabolism plays an important role in many cellular processes including energy production, immune function, and purine and pyrimidine synthesis. Cancer cells therefore require increased AA uptake and undergo metabolic reprogramming to satisfy the energy demand associated with their rapid proliferation. Like many other cancers, myeloid leukemias are vulnerable to specific therapeutic strategies targeting metabolic dependencies. Herein, our review provides a comprehensive overview and TCGA data analysis of biosynthetic enzymes required for non-essential AA synthesis and their dysregulation in myeloid leukemias. Furthermore, we discuss the role of the general control nonderepressible 2 (GCN2) and-mammalian target of rapamycin (mTOR) pathways of AA sensing on metabolic vulnerability and drug resistance.

Signal transducers and activators of transcription 5A and 5B (STAT5A and STAT5B) are two closely related STAT family members that are crucial downstream effectors of tyrosine kinase oncoproteins such as FLT3-ITD in acute myeloid leukemia (AML) and BCR-ABL in chronic myeloid leukemia (CML). We recently developed and reported the synthesis of a first molecule called 17 f that selectively inhibits STAT5 signaling in myeloid leukemia cells and overcomes their resistance to chemotherapeutic agents. To improve the antileukemic effect of 17 f, we synthesized ten analogs of this molecule and analyzed their impact on cell growth, survival, chemoresistance and STAT5 signaling. Two compounds, 7 a and 7 a\', were identified as having similar or higher antileukemic effects in various AML and CML cell lines. Both molecules were found to be more effective than 17 f at inhibiting STAT5 activity/expression and suppressing the chemoresistance of CML.

OBJECTIVE: Myeloid leukemias (MLs) are clonal stem cell disorders affecting myeloid lineage cells. Advances in cytogenetic and molecular studies partially disclosed the mystery about risk factors and pathophysiology of MLs. Regarding incidence, risk factors, response to treatment, and overall survival of patients, research showed differences among different countries. However, the Western registry data are the basis for the documented description of MLs in medical textbooks. This research aimed to study MLs in Middle Eastern health centers. Egypt has the highest population in the Middle East; furthermore, 96.6% of the population is native Egyptians; accordingly the study focused on Egypt.
METHODS: Data of 468 patients with MLs were collected from hospital records at two big tertiary health centers. They were grouped into group 1 (chronic myeloid leukemia, CML) and group 2 (acute myeloid leukemia, AML); the latter was subgrouped into 2a (primary AML) and 2b (secondary AML).
CONCLUSIONS: The median age of patients was 43 years; males predominate in group 2a and females in groups 1 and 2b. 37.2% of group 1 patients were treated with Gleevec. Hematopoietic stem cell transplantation was planned for only 5% of group 2 and 18% relapsed. Of groups 1 and 2 patients, 25% and 12%, respectively, stopped follow up, and 15% and 35% died. ORR and overall survival were 53%, 27% and 7%, 0.4% for groups 1 and 2, respectively. Conclusively, this study showed a young age of ML patients, with female predominance in CML, and poor outcome. This reflected racial, ethnic and risk factor differences in incidence of MLs.

Our aim is to assess the incidence of second cancer in long-time surviving primary mediastinal B-cell lymphoma (PMBCL) patients treated with combined radiochemoimmunotherapy (standard methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin with rituximab and mediastinal radiation therapy at a dose of 30 to 36 Gy). For this purpose, 92 points were evaluated. After a median overall survival of 137 months (range 76-212), we recorded second cancer in 3 of 80 long-surviving patients (3.75%) with cumulative incidence of 3.47% at 15 years and 11% at 17 years, with a 17-year second cancer-free survival of 82%. We observed 2 papillary thyroid cancers with a standardized incidence ratio (SIR) of 7.97 and an absolute excess risk (AER) of 17. 84 and 1 acute myeloid leukemia (AML) with an SIR of 66.53 and an AER of 10.05. No breast cancer occurred. Although we should take into account the limits of the proposed statistical analysis, combined modality treatment was related to a significant SIR and AER for thyroid cancer and acute myeloid leukemia.

During the past few years, a number of molecular markers have been developed in clinical hematology, most of them related to specific gene defects. However, there is also an unmet need to develop novel serologic parameters to improve diagnostics and prognostication in daily practice. Among these, the serum tryptase appears to be a most reliable biomarker of myeloid neoplasms. Elevated tryptase levels are found in subgroups of patients with mastocytosis, myelodysplastic syndrome, myeloproliferative neoplasm, acute myeloid leukemia, chronic myeloid leukemia and chronic eosinophilic leukemia. In these patients, the tryptase level is of diagnostic and/or prognostic significance. In mastocytosis, an elevated tryptase level is a minor criterion of systemic disease and in BCR-ABL1(+) chronic myeloid leukemia, elevated tryptase at diagnosis correlates with treatment responses and overall survival. In patients with elevated tryptase, the enzyme also serves as follow-up parameter and can be employed to measure treatment-responses. In the current article, we review and update the perspectives of tryptase and provide recommendations for use of this conventional biomarker in daily practice.