Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm, classically described as triphasic disease (chronic, accelerated, and blast). Despite the significant efforts made by different groups to optimize treatment and outcome, there are still unmet needs and unanswered questions. Ophthalmologic manifestations are among the therapeutic challenges. The best available therapy for patients presenting with ophthalmologic manifestations is still unclear. Here we present two cases of CML (chronic phase) with ophthalmologic manifestations as initial presentation, trying to shed light on this important type of presentation and proposing recommendations for hematologists in view of the current literature.

BACKGROUND:In Primary Myelofibrosis (PMF; a clonal disorder arising from the neoplastic transformation of early hematopoietic stem cells) patients, spinal cord compression (SCC) is a common complication or even a presentation symptom due to extramedu...

Hairy cell leukemia (HCL) is rare type of leukemia. This neoplasm is well-known to present with pancytopenia and splenomegaly. HCL is associated with BRAF mutation in 100% of cases. It is also associated with hematological and oncological malignancies such as melanoma and papillary thyroid cancer. Although the association of both cancers (HCL and papillary thyroid cancer) with BRAF mutation is well established in the literature, as far as we know it has not been reported before in the same patient. Here we report 48-year-old male diagnosed with HCL and papillary thyroid cancer and who is BRAF positive in both diagnostic tissues.

Post cytotoxic myeloid neoplasms signify a heterogenous pool of poorly understood hematologic neoplasms with unfortunate survival and ineffective therapies. There is a lack of consensus on prognostic indicators, primarily due to the heterogenous disease spectrum encompassing different pathological, cytogenomic and original disease variables. This retrospective, single-center study over 10 years duration on MN-pCT cases diagnosed at NCCCR, a member of Hamad Medical Corporation. The study aimed to analyze clinicopathologic and cytogenomic characteristics, identify key prognostic predictors, and assess their impact on mortality through univariate and multivariate analyses. We identified 42 MN-pCT patients, noting a 31.7% prevalence of autoimmune diseases as primary condition, which is higher than previously reported. TP53 was the most frequently mutated gene, found in 28.6% of tested cases. Significant determinants of a shorter latency period included prior exposure to alkylating agents and TP53 positivity (by NGS or IHC) (P < 0.05). Younger patients (≤ 50 years) exhibited longer survival (P = 0.018). Poor prognostic markers included dyserythropoiesis (P = 0.045), MPO downregulation (P = 0.026), mutated TP53 (NGS/IHC) (P = 0.004), and failure to achieve CR (P = 0.002). Multivariate Cox regression identified both a latency period of ≥ 5 years and TP53 positivity (detected by either NGS or IHC) as statistically significant independent factors associated with reduced overall survival (P < 0.05). It is important to highlight that P53 mutation by NGS was a common parameter identified by the multivariate analysis that adversely impacted both MN-Pct survival and OS. This study stands as a significant contribution to our understanding of the clinicopathologic characteristics and prognostic predictors of MN-pCT in MENA region. It also underscores the existence of adverse prognostic factors, extending beyond the genetic influences and emphasizing the necessity of recognizing it as a distinct entity in the future classification systems.

Background: Wide application of genome sequencing technologies has highlighted extensive genetic diversity in Acute Myeloid Leukemia (AML), yet the specific roles of individual genes remain unclear. This systematic review and meta-analysis aims to provide robust evidence for the prognostic impact of somatic gene mutations in de novo AML patients, while also exploring the prevalence of these mutations. Methods: Eligible studies were identified from PubMed and Scopus, with a focus on those reporting the prognostic influence of somatic gene mutations on overall survival (OS) or relapse-free survival (RFS) when compared to wild-type carriers. We calculated the pooled prevalence with 95% confidence intervals to assess the frequency of these mutations, and the pooled Hazard Ratio (HR) to compare OS and RFS associated with specific gene mutations. Results: We evaluated 53 somatic gene mutations using 80 studies, involving 20,048 de novo AML patients. The analysis revealed that the most prevalent affected genes were NPM1 (27%), DNMT3A (26%), and FLT3-ITD (24%). Mutations in CSF3R, TET2, and TP53 were significantly associated with poorer OS or RFS (p < 0.05). Sensitivity analysis confirmed that ASXL1, DNMT3A, and RUNX1 mutations were consistently linked to inferior OS or RFS. In contrast, CEBPAdm mutations were associated with favorable OS [HR = 0.39 (0.30–0.50)] and RFS [HR = 0.44 (0.37–0.54)]. Subgroup analysis showed that FLT3-ITD mutations were consistently associated with worse OS or RFS across all subgroups, though no significant subgroup differences were noted. No significant impact on OS or RFS was observed for mutations in GATA2, FLT3-TKD, KRAS, NRAS, IDH1, and IDH2. Conclusions: These findings provide critical insights into AML prognosis, aiding clinical decision-making and improving risk stratification strategies.

Background: Outcomes in chronic myeloid leukemia (CML) remain heterogeneous despite effective BCR::ABL1 tyrosine kinase inhibitors (TKIs). Somatic mutations in epigenetic regulators, particularly additional sex combs like 1 (ASXL1), have been implicated in adverse prognosis, but their clinical impact in CML has not been systematically defined. Methods: A systematic review was conducted using CINAHL, EMBASE, MEDLINE Ultimate, and PubMed from inception through August 2025. A total of 1,339 records were identified; after duplicate removal and screening, 11 studies met inclusion criteria and were included in qualitative synthesis and meta-analysis. Eligible studies included adult and pediatric patients with chronic and advanced phase (accelerated or blast) CML with ASXL1 mutation status assessed using validated molecular methods. Outcomes included molecular response, cytogenetic response, survival, and treatment resistance. Random-effects models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the I² statistic. Results: Across included studies, ASXL1 mutations were detected in approximately 16% of patients. At 12 months, ASXL1-mutated patients had significantly lower odds of achieving major molecular response (MMR) compared with ASXL1–wildtype patients (OR 0.29; 95% CI 0.16–0.51; p< 0.0001; I²=30%). No statistically significant difference was observed in complete cytogenetic response (CCyR) (OR 0.30; 95% CI 0.02–5.31; p=0.41; I²=68%). Compared with patients harbouring other non-ASXL1 somatic mutations, ASXL1 mutation was not associated with a significant difference in MMR (OR 0.49; 95% CI 0.23–1.05; p=0.067; I²=0%). Conclusions: ASXL1 mutations are associated with inferior molecular response to TKI therapy in CML, supporting their role as an adverse prognostic biomarker. These findings highlight the potential value of incorporating myeloid mutation profiling into future CML risk-stratification strategies.