Acute Promyelocytic Leukemia

P=N/A, N=400, Active, not recruiting, Groupe Francophone des Myelodysplasies | Recruiting --> Active, not recruiting | Trial completion date: Oct 2022 --> Jul 2026 | Trial primary completion date: Oct 2020 --> Jul 2026

The rare genetic co-occurrence of t(15;17)/PML::RARA and t(9;22)/BCR::ABL1 translocations may be identified in a single patient with acute promyelocytic leukaemia (APL).Successful induction using all-trans retinoic acid (ATRA) together with imatinib achieved effective control of both leukemic clones.The patient demonstrated rapid haematologic remission and favourable clinical recovery, suggesting a positive outcome with this therapeutic approach.

This case brings to light the diagnostic challenges posed by variant APLs that may demonstrate divergent morphologic and phenotypic features and carry translocations that render the routine PML::RARA fusion-based methodologies futile. Accurate diagnosis requires a high index of suspicion and a comprehensive multifaceted diagnostic strategy that encompasses morphologic assessment, immunophenotypic analysis, RARA break-apart probe analysis supplementing traditional fusion probe techniques, conventional karyotyping, and advanced molecular fusion testing.

We propose that such a low-intensity regimen may be suitable for older patients with AML, who are unfit for intensive chemotherapy. We also present data indicating that PRI5202 induces myeloid differentiation in blasts from patients with myelodysplastic syndrome (MDS), and we propose to further investigate PRI5202 as a differentiation therapy for patients suffering from MDS.

MSC-l levels were lower in patients receiving myeloablative conditioning compared with non-transplanted patients, suggesting transplant intensity may influence MSC dynamics. Higher post-treatment MSC-l proportions are associated with poorer survival, independent of ELN risk and age, supporting their potential as a prognostic biomarker in AML.

This study confirmed well-known gene-disease associations in myeloid malignancies but found no significant link between parvovirus B19 infection and specific somatic mutations or disease subtypes. These findings suggest that B19 infection may be incidental, underscoring the need for larger-scale studies to clarify its clinical relevance in patients with myeloid malignancies.

Additionally, YW3-56 suppressed the downstream mTOR pathway, inducing caspase-3/PARP-mediated apoptosis and inhibiting cell proliferation. Our study demonstrated that YW3-56 exerts multimodal antileukemic effects in APL by simultaneously targeting PAD4-mediated epigenetic regulation, AKT-driven metabolic reprogramming and cellular differentiation, highlighting PAD4-AKT signaling as a promising target for APL combination therapy.

EWSR1 could be a powerful prognostic indicator for clinical strategy selection in AML. The prediction model may effectively predict the OS of non-APL AML.

P1, N=66, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed

In recent years, a novel type of tripartite retinoic acid receptor (RAR) fusion genes has been identified in atypical APL (aAPL), exhibiting distinct structural characteristics and pathogenic mechanisms compared to the classical bipartite fusion. This article systematically introduces relevant content in this field: it begins by outlining the long-standing scientific puzzle of inconsistent clinical resistance versus in vitro sensitivity in aAPL patients; subsequently, it describes the discovery process and structural features of tripartite fusion genes in all RARG and specific RARA-related cases, and elucidates the key molecular mechanism by which tripartite fusion leads to all-trans retinoic acid (ATRA) resistance at the protein conformational level; finally, the discovery of transposon involvement in the formation of tripartite fusions and its implications for the mechanism of fusion gene are discussed.

P1, N=12, Completed, SDK Therapeutics, Inc. | Phase classification: P1/2 --> P1

In summary, our data confirm that CEBPA bZIPinf mutation is an independent factor of favorable prognosis in AML patients.