Acute Promyelocytic Leukemia

Conversely, the N-to-C synthesis method proceeded efficiently without cysteine protection, thereby simplifying the workflow and reducing the number of purification steps. This research presents a reliable and accessible method for the complete chemical synthesis of RNF4, addressing significant challenges in synthesizing large proteins and opening up new opportunities for future biological research.

TCN augments the differentiation-inducing activity of ATRA and promotes partial myelomonocytic differentiation, even in ATRA-resistant AML cells. Combination of TCN with established differentiation therapy may provide a strategy to overcome differentiation blockade in AML.

The absolute mortality risk reduction was 16%, yielding a number-needed-to-treat of seven. Early ED ATRA initiation substantially improved survival in PML-RARA-confirmed APL.

Future directions include integrated multi-omics analyses to comprehensively map cellular state transitions, studies of natural regression phenomena to identify reversion mechanisms, advanced nanodelivery systems for targeted therapy, and synthetic biology approaches creating intelligent therapeutic systems. By redirecting rather than destroying cancer cells, reversion therapy offers the potential for reduced toxicity and resistance, potentially transforming cancer from a deadly disease to a manageable condition.

Compared with non-APL-AML patients, APL patients (PML-RARα (S-type) and PML-RARα (L-type)) exhibit unique immunophenotypic changes. The expression frequencies of CD56, CD2, CD34, and CD200 in leukemia cells are significantly correlated with the OS of APL patients, and the high expression of these indicators before treatment may be an adverse prognostic factor for APL patients.

The 3-year overall survival rates and event-free survival (EFS) rates were 80.7% and 69.4%, respectively. Multivariate Cox regression analysis revealed that gene MLL rearrangement (excluding MLL-AF9) (HR=3.071, 95%CI: 1.024-9.205) and positive molecular MRD after Induction Course Ⅱ therapy (HR=5.571, 95%CI: 1.244-24.957) were risk factors for EFS in pediatric AML patients.

The patient achieved sustained remission following risk-adapted AML chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case underscores three critical points in pediatric AML: (1) the essential role of integrated molecular profiling in resolving morphologic ambiguities to prevent misclassification; (2) the complex prognostic impact of FLT3-ITD/NPM1 co-mutations in childhood AML; and (3) the potential therapeutic efficacy of allo-HSCT for rare fusion-driven subtypes.

Multivariate analysis confirmed high bZIP-domain VAF and DNMT3A mutation as independent risk factors. Our results confirm that the bZIP-domain VAF of CEBPA mutations is a more effective predictor of relapse than the maximum VAF, offering a valuable tool for the early identification of patients at high risk of relapse.

(3) Clinical evidence confirms that ATRA combined with arsenic trioxide or epigenetic modulators achieves high remission rates in APL and selected AML subtypes...(4) ATRA-based combination therapies represent a promising strategy to extend differentiation therapy beyond APL. This review, authored solely by the investigator, highlights molecular targets and potential enhancers warranting further clinical evaluation in AML.

APL mice had significantly higher levels of thrombin-antithrombin complexes compared with AML mice. These leukemia mouse models can be used to understand how the hemostatic system is dysregulated in leukemia.

Notably, demethylation therapy induced sustained complete remission in patients with refractory recurrent APL during experimental treatment. Our findings underscore the critical role of ALDH1A3 in leukemogenesis and highlight its potential as a therapeutic target in APL.

Whenever there is a suspicion of APL, ATRA should be started, given its potential severity. There are few cases with non-APL with this morphology but are rarely described in acute leukemia with myelodysplasia related changes.