Mixed-phenotype leukemia (MPAL) is a type of acute leukemia in which the blast population shows mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. MPALs are rare and carry a poor prognosis, thus, often pose both a diagnostic and therapeutic challenge. Conventionally, the diagnosis of MPAL requires either a single blast population with a lineage-defining phenotypic expression of multiple lineages (myeloid, B-cell and/or T-cell) (biphenotypic) or two distinct blast populations that each independently satisfy criteria for designation as AML, B-ALL, and/or T-ALL (bilineage). Given the rarity of MPAL, minimal studies have been performed to describe the genomic landscape of these neoplasms. IRB approval was obtained. Central MCC database was searched for any patient with a diagnosis of acute undifferentiated leukemia (AUL), acute leukemia of ambiguous lineage (ALAL), and MPAL. All patient diagnoses were manually reviewed by a hematopathologist to confirm the diagnosis of MPAL. Genomic and molecular data were collated from the EMR and bioinformatically from MCC genomics repositories. Twenty-eight patients with MPAL were identified. Thirteen were female and 15 were male. Average age was 56 years old (range = 28–81). Ten cases were biclonal and 18 were biphenotypic. Diagnoses were as follows: B/myeloid (n = 18), T/myeloid (n = 9), and T/B (n = 1). Cytogenetic analysis (Karyotype +/− FISH) was available for 27 patients. The most frequent recurrent abnormalities were complex karyotype (n = 8), BCR/ABL1 translocation (n = 6), Del 5q/−5 (n = 4), Polysomy 21 (n = 4). Mutational analysis was available for 18 patients wherein mutations were detected in 45 unique genes. The most frequently mutated genes were TP53 (7), RUNX1 (6), WT1 (4), MLL2 (3), FLT3 (3), CBL (2), ASXL1 (2), TET2 (2), MAP3K6 (2), MLL (2), and MAP3K1 (2). Targetable or potentially targetable biomarkers were found in 56% of cases. Overall survival was 19.5 months (range = 0–70 m). Ten patients were treated with an allogeneic stem cell transplant and had superior outcome (p = 0.0013). In one the largest series of MPAL cases to date, we corroborate previous findings with enriched detection of RUNX1 and FLT3–ITD mutations along with discovery of unreported mutations (MAP3K) that may be amenable to therapeutic manipulation. We also report the frequent occurrence of AML with MDS-related changes (AML-MRC)-defining cytogenetic abnormalities (26%). Finally, we show that those patients that received stem cell transplant had a better overall survival. Our findings support the need to genomically profile MPAL cases to exploit opportunities for targeted therapies in this orphan disease with dismal prognosis.

Chorioamnionitis generates prostaglandin E₂ and F_2α, promoting fetal membrane rupture, cervical ripening, and uterine contractions. 15-hydroxyprostaglandin dehydrogenase (HPGD) contributes to pregnancy maintenance by inactivating prostaglandins. The role of decidual cells in regulating HPGD expression at the maternal-fetal interface was investigated. HPGD immunostaining was primarily detected in anchoring villi and choriodecidual extravillous trophoblasts (EVTs) of first, second and third trimester. Chorionic EVTs adjacent to decidua parietalis exhibited significantly higher HPDG levels than those adjacent to amnion. HPGD HSCORE levels were significantly lower in choriodecidua from chorioamnionitis vs. gestational age-matched controls (Mean±SEM; 132.6±3.8 vs. 31.2±7.9; P<0.05). Conditioned media supernatant (CMS) from in vitro decidualized term decidual cells (TDCs) upregulated HPGD levels in EVTs differentiated from human trophoblastic stem cells, primary trophoblasts and HTR8/SV^neo cells. However, CMS from 5 μg/mL LPS or 10 ng/mL IL-1β pretreated TDC cultures downregulated HPGD levels in HTR8/SV^neo cultures. Similarly, direct treatment of HTR8/SV^neo cultures with LPS or IL-1β significantly reduced HPGD levels vs. control (0.57±0.1 or 0.47±0.1, vs. 1.03±0.03; P<0.05) but not in TDC-CMS pretreated HTR8/SV^neo cultures. Collectively, the results uncover a novel decidual cell-mediated paracrine mechanism which stimulates levels of trophoblastic HPGD, whose function is to inactivate labor-inducing prostaglandins, thereby promoting uterine quiescence during pregnancy. However, infectious/inflammatory stimuli in decidual cells cause a paracrine inhibition of trophoblastic HPGD expression, increasing PGE₂/F_2α levels, thereby contributing to preterm birth.

Blood diseases and disorders, including leukemia and infectious diseases of red blood cells, pose significant diagnostic challenges due to their complex presentations and reliance on time-consuming cytomorphological analysis to detect subtle morphologic features. While microscopic examination remains the gold standard in their diagnosis, its dependence on expert interpretation high-lights the need for advanced methods to enhance the diagnostic workflow. Recently, deep learning (DL) methods have shown promise in medical imaging by automating and improving accuracy. However, these approaches often require large, annotated datasets, which are scarce for rare diseases, and they often face interpretability issues, limiting their integration into clinical practice. In this study, we present a novel framework that integrates topological features with state-of-the-art DL techniques to enhance the analysis of cytomorphological images for diagnosing blood disorders. By combining global topological information with the localized patterns captured by DL models, our approach improves diagnostic accuracy while ensuring robustness, interpretability, and reproducibility. Experimental results demonstrate that the inclusion of topological features not only enhances model performance but also proves particularly effective in limited data settings. This methodology addresses critical limitations of existing techniques, advancing the classification and diagnosis of blood disorders while improving efficiency and reliability in medical imaging workflows.