Acute Promyelocytic Leukemia

He underwent haploidentical transplantation using post-transplant cyclophosphamide (PTCy) after conventional chemotherapy and maintained long-term remission. This case highlights the importance of a morphological diagnosis and allogeneic hematopoietic stem cell transplantation (allo-HSCT) in APL with t(11;17)(q23.2;q21.2).

BP is an effective adjunct to ATO therapy, counteracting gut dysbiosis, intestinal damage, and the immune microenvironment while synergistically improving antileukemic efficacy. Targeting the gut-leukemia axis with BP represents a promising strategy for improving the precision and safety of APL treatment.

While differentiation therapy revolutionized acute promyelocytic leukemia (APL) with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), its extension into non-APL AML has been limited until recent targeted agents...IDH1/2 inhibitors (ivosidenib, enasidenib, olutasidenib) yield overall response rates (ORRs) of 30-94% in AML with DS in 10-19%. Menin inhibitors (revumenib, ziftomenib, enzomenib, bleximenib) achieve ORRs of 33-88% in KMT2A-rearranged or NPM1-mutated AML, with DS in 10-25% and QT prolongation as key toxicities. FLT3 inhibitors (gilteritinib, quizartinib) improve survival in FLT3-mutated AML with DS in 1-5%...Improved recognition of DS and rational combination approaches will be essential to maximize the therapeutic benefit. Future research should address mechanisms of resistance and biomarkers to achieve cures beyond APL.

P=N/A, N=202, Active, not recruiting, ECOG-ACRIN Cancer Research Group | Trial completion date: Dec 2025 --> Dec 2027

After treatment with all-trans retinoic acid and arsenic trioxide, he developed localized penile ulcers resistant to antibiotics. The ulcers improved following chemotherapy with daunorubicin and azacitidine. This case highlights penile ulcerations as a rare manifestation of leukemia cutis in APML, underscoring the importance of considering leukemic infiltration in differential diagnosis of genital ulcers when infectious causes are excluded.

Combination regimens such as retinoic acid with entinostat and doxorubicin achieve potent antitumor synergy in preclinical models. Notably, emerging methylation-based classifiers that identify retinoid-responsive triple-negative breast cancer subsets, together with the paradoxical pro-tumorigenic effects of stromal RARβ, underscore the novelty and translational significance of integrating tumor-intrinsic and microenvironmental determinants of retinoid sensitivity. Together, these approaches may help re-establish functional retinoid signaling and realize the therapeutic potential of retinoic acid in breast cancer.

Induction therapy with all-trans-retinoic acid and arsenic trioxide resulted in hematologic remission...Atypical clinical trajectories should prompt careful assessment of marrow morphology and immunophenotypic features. Continued characterization of such cases may refine diagnostic criteria and direct individualized approaches to therapy.

P3, N=158, Active, not recruiting, Children's Oncology Group | Trial completion date: Sep 2025 --> Jun 2029

Early diagnosis of acute promyelocytic leukemia (APL), driven by PML-RARA oncoprotein, is vital for survival, as delays can cause fatal coagulopathy without prompt therapeutic intervention of all-trans retinoic acid and arsenic trioxide...Pharmacological inhibition of TGF-β1 ligand using luspatercept reduced SMAD phosphorylation and PDPN expression, indicating TGF-β/SMAD transcriptionally regulates PDPN. Additionally, ELISA-based serum profiling showed significantly elevated TGF-β1 levels in APL patients compared to non-APL AML (p < 0.0001). These findings identify PDPN overexpression as a downstream consequence of TGF-β/SMAD signaling and highlight its potential as a diagnostic biomarker for APL.

This case of APL with coexisting ider(17) and FLT3-ITD mutations exhibited an aggressive course and resistance to standard treatment. These findings suggest that such patients may require intensified therapeutic strategies and closer monitoring.

We report a 49-year-old male patient with a normal serum uric acid and recent diagnosis of acute promyelocytic leukemia (APL) who developed a severe polyarticular gout flare during treatment with arsenic trioxide (ATO)...The gout flare in our patient was initially treated with high-dose intravenous glucocorticoids with no clinical response and was subsequently treated with interleukin-1β receptor blockade, which resulted in complete clinical resolution of his gout. Our case offers insights into inflammatory pathways in gout, including the evolving role of ROS in autoinflammation.

Both genetic knockdown and pharmacological inhibition of PSMD14 recapitulate EB's effects, confirming its essential role in leukemia cell survival and proliferation. Collectively, these findings uncover a previously unrecognized PSMD14-AKT1/CDK4 regulatory axis in leukemia and position EB as a promising chemical probe and lead compound for the development of targeted covalent inhibitors against oncogenic DUBs.