RUNX1 (RUNX Family Transcription Factor 1)

We recommend routine monitoring with quarterly complete blood counts and annual bone marrow biopsies to monitor for changes and transformation to HM. (NCT03854318).

IL-18 emerged as a critical inflammatory mediator, with elevated plasma levels correlating with the transformation to high-grade fibrosis (reticulin grades 2-3). Functional assays confirmed that the IL-18 stimulation of mesenchymal stromal cells induced fibrotic transformation, emphasizing its role as a biomarker and target.

AML with KMT2A-PTD shows distinctive immunophenotypic features with increased CD123 and aberrant CD25 expression, both associated with FLT3-ITD. These markers may have diagnostic and therapeutic relevance in this AML subtype.

Identification of these germline mutations is critical as MNs with germline predisposition dictate specific therapeutic strategies-particularly for hematopoietic stem cell transplantation (HSCT)-and require genetic counseling and surveillance for at-risk relatives. Accurate diagnosis often requires non-hematopoietic germline DNA testing, which provides important biological insights into the development of different myeloid neoplasms and directs personalized patient care.

This study revealed that patients aged ≥50 years displayed more complex genetic aberration profiles and experienced significantly poorer prognoses compared to their younger counterparts. These findings provided novel insights for optimizing treatment strategies for middle-aged and elderly AML patients in the Chinese population.

Here, we present two cases of pDC-AML with B-cell marker expression in which RUNX1 aberrations were not identified. Although previously we speculated on the role of RUNX1 in the aberrant expression of B-cell markers such in cases, the absence of RUNX1 lesions in the current cases supports the potential inherent ability of pDCs to express B-cell markers during maturation.

Finally, a multipronged validation strategy using in vitro and in vivo systems confirms the GF-NEOs presentation through mass spectrometry-based proteomics and immunopeptidomics. Multiple GF-NEOs encoded by two versions of the ETV6-RUNX1 fusion were validated, paving the way for targeted immunotherapy development.

Patients with JAK2V617F- and CALR-unmutated ET tend to present at a younger age and exhibit a lower incidence of thrombosis compared to those with JAK2V617F-mutated ET. The application of WES enabled the detection of uncommon and potential driver mutations in JAK2V617F- and CALR-unmutated ET.

Serial assessments were performed before and during treatment with bortezomib and dexamethasone for MM, and later with daunorubicin/cytarabine for AML. It demonstrates the earliest events in pDC-AML evolution. Furthermore, the immature immunophenotype raises the question of appropriate treatment, since a diagnosis of acute undifferentiated leukemia can be established.

Current research has revealed that ASXL1 mutations in MDS predict demethylating agents (HMAs) resistance, the combination of HMAs and Venetoclax (VEN) achieved an ORR of 87%. DNMT3A R882 mutations induce decitabine sensitivity via hemi-methylated enhancer trapping, and TET2 mutations enhance HMAs efficacy only in ASXL1 wild-type contexts (ORR 62.1% vs. co-mutated 19%). RUNX1 aberrations reduce chemotherapy responses (18.9% ORR in high-risk MDS) through DNA repair impairment, while BCOR/EZH2 loss drives cytarabine resistance. TP53 multi-hit lesions correlate with poor survival (OS <12 months) but respond to eprenetapopt-azacitidine (ORR 73%), and IDH1/2 inhibitors achieve durable remissions (ivosidenib ORR 83.3%, mOS 35.7 months). In this paper, we systematically illustrate the correlation between key gene mutations and the response to HMAs, chemotherapy and targeted therapies in MDS patients. This article summarizes the current evidence on gene mutations as predictive biomarkers and discusses the direction of individualized therapy.

Subsequent comprehensive integration of clinical history, repeated bone marrow assessment, cytogenetics, fluorescence in situ hybridization (FISH), and extended immunohistochemistry(IHC) revealed the tumor to be a myeloid sarcoma (MS), representing an extramedullary relapse of his underlying AML. This case underscores the diagnostic pitfalls of MS, particularly within the central nervous system (CNS), and highlights the critical importance of considering MS in patients with a history of AML, especially those with genetic profiles predisposing to extramedullary disease, even when pathology initially suggests lymphoma.

The high diagnostic coverage and rapid turnaround of the FISH-based approach underscore its value as a reliable and efficient diagnostic tool in newly diagnosed ALL. The authors have confirmed clinical trial registration is not needed for this submission.