Integrating the detection, quantification, and allelic characterization of KMT2A partial tandem duplication (KMT2A-PTD) into DNA sequencing tests may be prognostically valuable for patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML), according to research published in Blood Advances.

Previous research has demonstrated that KMT2A-PTD — which is noted in up to 10% of patients with AML or MDS — is a predictor of poor outcomes in this patient population. In particular, high RNA levels of KMT2A-PTD have been tied to inferior survival, though the genomic underpinnings of this finding were previously not established.

Historically, clinicians have opted to evaluate RNA KMT2A-PTD levels when making prognostic estimates. For this study, researchers aimed to determine whether integrating KMT2A-PTD into standard DNA next-generation sequencing (NGS) panels is of prognostic utility for patients with MDS or AML.

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Overall, 94 patients with AML or MDS and KMT2A-PTDs were identified using NGS. Of these patients, 16% had complex secondary events, such as copy-neutral loss of heterozygosity and selective gain via the KMT2A-PTD allele.

KMT2A-PTD burden was higher in patients with AML than in those with MDS. High PTD copy ratios suggesting complexity were more common in AML than in MDS. Complexity was linked with greater PTD RNA expression and a greater risk of relapse and secondary transformation.

KMT2A-PTD was exclusively identified in patients with MDS/AML, and subclonal development of allelic complexity was closely correlated with disease progression, providing a genomic mechanism for the prognostic relevance of high KMT2A-PTD RNA levels,” the researchers wrote. “Our approach can be incorporated into standard panel-based DNA sequencing and may be deployed in clinical settings to improve prognosis at diagnosis, surveillance of molecular dynamics at progression and after treatment, and predict response to targeted therapies.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ disclosures. 


Tsai HK, Gibson CJ, Murdock HM, et al. Allelic complexity of KMT2A partial tandem duplications in acute myeloid leukemia and myelodysplastic syndromes. Blood Adv. 2022;6(14):4236-4240. doi:10.1182/bloodadvances.2022007613

This article originally appeared on Hematology Advisor