BackgroundDDX3X and MLLT10 genes are located on chromosomes X and 10, respectively. In a study of 2,080 children and young adults (0-30 years) with AML, MLLT10 rearrangements were reported in 6.1% of cases. KMT2A was the most common fusion partner, occurring in 81.9% of cases. In contrast, DDX3X::MLLT10 was found in approximately 0.1% of the cohort. (Abla et al., 2024) The clinical and pathological characteristics of adult AML with DDX3X::MLLT10 are not well characterised, detailed in only two cases published to date.

Method A case report and literature review.

Results A 27-year-old female presented with a two-week history of lethargy and bleeding gums and was diagnosed with acute myelomonocytic leukaemia (AMML). The karyotype was 46,X,t(X;10)(p10;q10)[2]/47,idem,+mar[18] and a KRAS c.38G>A p.(Gly13Asp) variant was identified at a frequency of 27.89% without FLT3 and NPM1. Induction chemotherapy with idarubicin and cytarabine (“7+3”) was commenced. Bone marrow examination (BME) on day 31 of treatment showed no response, with a 46,X,t(X;10)(p10;p10)[1]/47,sl,+mar[26]/46,XX[3] karyotype, KRAS c.38G>A p.(Gly13Asp) and SMARCA4 c.3325A>G p.(Met1109Val) variants at read frequencies (VRF) of 43 and 39%, respectively. Targeted RNA fusion sequencing reported DDX3X::MLLT10 exon5::exon9 (NM_001356.4::NM_001324297.1).

She commenced salvage fludarabine, cytarabine, idarubicin and filgrastim (FLAG-Ida) therapy with BME on day 34 of treatment showing morphologic leukaemia-free state (MLFS). However, repeat BME on day 48 confirmed refractory disease. She then commenced bridging venetoclax/azacitidine (Ven/Aza) therapy with a plan for allogeneic haematopoietic stem cell transplant. BME on day 22 of treatment showed no response. NGS redemonstrated similar findings to those of the previous BM, including DDX3X::MLLT10, as well as KRAS and SMARCA4 at VRFs of 41% and 46%, respectively. Treatment was complicated by neutropenic sepsis, respiratory failure, and intracranial haemorrhage. She passed away after transitioning to comfort care.

DiscussionDDX3X::MLLT10 is not an AML-defining genetic aberration in the 2022 World Health Organization (WHO) classification. The gene fusion has also been reported in three percent of adults with T-acute lymphoblastic leukaemia (T-ALL) and in a case of triphenotypic acute leukaemia.(Brandimarte et al., 2014; Leitinger et al., 2021)

Only three cases of AML with DDX3X::MLLT10 have been reported to date, including the present case.(Nilius-Eliliwi et al., 2022; Li et al., 2025) They highlight important observations and unmet clinical needs in this rare entity. Firstly, all cases occurred in younger adults (21-27 years). Secondly, there is significant heterogeneity in the pathological characteristics, particularly the genomic findings. Notably, other adverse prognostic markers were observed, namely FLT3-ITD and complex karyotype, each identified in one case. Other associated molecular findings include variants in JAK2 exon 14/16, SH2B3, and CEBPA (biallelic heterozygous).

Most importantly, a poor prognosis, including resistance to multiple lines of therapy, is observed. According to the 2022 ELN risk stratification, DDX3X::MLLT10 carries an intermediate risk, as it is neither favourable nor adverse. However, the clinical course and treatment response seen in these cases are concordant with the poor outcomes reported in children and young adults with AML harbouring MLLT10 rearrangements.(Abla et al., 2024) Given the poor outcomes, there may be an unmet need for more effective therapies.

Of note, given the location of DDX3X and MLLT10 genes on chromosome Xp11.4 and 10p12.31, respectively, there is a slight discrepancy with the karyotype finding of t(X;10)(p10;p10) in this case, which may be due to the resolution. In Li et al.'s study, t(X;10)(p11.2;p11.2) was reported.

Conclusion This is the third case detailing AML with DDX3X::MLLT10 in adults. This case supports the poor prognosis and chemoresistance reported with this entity. The case also highlights its genomic heterogeneity and extends the co-mutations to include KRAS and SMARCA4. However, more data are required for further characterisation. These findings may inform future iterations of AML classification and prognostication (e.g., WHO) in adults.

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2025
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