Among patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), KMT2A partial tandem duplication (KMT2A-PTD) detection, quantification, and allelic characterization may be prognostically valuable if integrated into DNA sequencing tests, 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 are known to be linked with inferior survival, though the genomic underpinnings of this finding were previously unestablished.

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 among patients with MDS or AML.

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

Compared with MDS, patients with AML had high KMT2A-PTD copy numbers, suggesting complexity; this was also linked with higher RNA expression. Complexity was further linked with 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 authors wrote in their report. “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: The study author(s) 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