CBFB-MYH11 fusion

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.

We identified remaining tumor clones in 6 patients with complete remission samples indicating incomplete eradication of the tumor clones. Here, we show that identifying the order of mutation acquisition can provide valuable insights into evolutionary history, offering a framework to improve drug selection in the era of targeted therapies.

With the routine use of next-generation sequencing (NGS) for gene fusion detection, more patients like this one should be diagnosed and treated accordingly. These cases illustrate the importance of a comprehensive molecular/cytogenetic diagnostic work-up.

An IGH::DUX4 fusion previously found by RNA-seq in Case 3 was not confirmed because DUX4, which has multiple pseudogenes, was refractory to OGM and WGS analyses. OGM is a fundamental tool that complements G-banding analysis in identifying complex SVs in leukemia samples, and WGS effectively closes the gaps in OGM mapping.

The VEN + HMAs regimen demonstrated considerable efficacy in the treatment of R/R AML patients, with both response rates and overall survival being influenced by distinct genetic features. These findings provide valuable insights into optimizing personalized treatment strategies for this challenging patient population.

P3, N=204, Completed, University of Ulm | Active, not recruiting --> Completed

P=N/A, N=400, Completed, Acute Leukemia French Association | Recruiting --> Completed

Subsequently, the type I CBFB::MYH11 fusion gene was identified through exhaustive exploration using RNA sequencing for fusion gene discovery. This exceptional case highlights the existence of a distinctive subtype of CBFB::MYH11 that may yield false-negative results in conventional chimeric fusion screening, thus emphasizing the indispensable utility of PCR primer modification, FISH, and RNA sequencing in the investigative process.

Paradoxically, CBFB::MYH11 expression was associated with increased RUNX1/2 expression, suggesting the presence of a sensor for reduced functional RUNX1 protein, and a feedback loop that that may attempt to compensate by increasing RUNX1/2 transcription. These findings may have broad implications for AML pathogenesis.

In the Phase II Trial REL AML 001 (EudraCT Number 2017-002094-18; ClinicalTrials ID: NCT 03686345) adult CBF leukemia patients treated with a continuation therapy with Midostaurin were included, and the measurable residual disease (MRD) was performed by molecular MRD assessment (qPCR) and multiparametric flow cytometric-MRD (MCF-MRD) assay... Although MCF-MRD assay showed lower sensitivity than CBF qPCR, MCF offered interesting informations about the dynamics of the abnormal clone size with time, evaluated as the increasing number of MRD clustering events, which may predict an impending relapse.

Exon 17 KIT mutations serve as an important predictor of relapse in RUNX1::RUNX1T1 pediatric AML. In addition, a high KIT VAF may predict poor outcomes in these patients. These results emphasize the need to incorporate KIT mutational analysis into risk stratification for pediatric CBF-AML.