Characteristics and outcome of patients with acute myeloid leukaemia and t(8;16)(p11;p13): results from an International Collaborative Study*

Abstract

Summary In acute myeloid leukaemia (AML) t(8;16)(p11;p13)/MYST3–CREBBP is a very rare abnormality. Previous small series suggested poor outcome. We report on 59 patients with t(8;16) within an international, collaborative study. Median age was 52 (range: 16–75) years. AML was de novo in 58%, therapy‐related (t‐AML) in 37% and secondary after myelodysplastic syndrome (s‐AML) in 5%. Cytogenetics revealed a complex karyotype in 43%. Besides MYST3–CREBBP, whole‐genome sequencing on a subset of 10 patients revealed recurrent mutations in ASXL1, BRD3, FLT3, MLH1, POLG, TP53, SAMD4B (n = 3, each), EYS, KRTAP9‐1 SPTBN5 (n = 4, each), RUNX1 and TET2 (n = 2, each). Complete remission after intensive chemotherapy was achieved in 84%. Median follow‐up was 5·48 years; five‐year survival rate was 17%. Patients with s‐/t‐AML (P = 0·01) and those with complex karyotype (P = 0·04) had an inferior prognosis. Allogeneic haematopoietic cell transplantation (allo‐HCT) was performed in 21 (36%) patients, including 15 in first complete remission (CR1). Allo‐HCT in CR1 significantly improved survival (P = 0·04); multivariable analysis revealed that allo‐HCT in CR1 was effective in de novo AML but not in patients with s‐AML/t‐AML and less in patients exhibiting a complex karyotype. In summary, outcomes of patients with t(8;16) are dismal with chemotherapy, and may be substantially improved with allo‐HCT performed in CR1.

A large co‐operative biological and clinical study to better understand and improve treatment of the rare t(8;16)(p11;p13) acute myeloid leukaemia

“…Hierarchical clustering of RNA expression data from a subset of MYST3‐linked AML samples showed that most MYST3‐linked AMLs grouped together and constituted a homogeneous subgroup of AML. Interestingly and perhaps relevant to the findings of Kayser et al ., 1 in 2017 Yu et al 7 . identified amplification of the MYST3 gene in breast cancer and showed that loss of MYST3 in oestrogen receptor (ER)‐positive breast cancer cell lines was associated with loss of expression of the oestrogen receptor.…”

“…Using chromatin immunoprecipitation (ChIP) they found that MYST3 binds to the ER α receptor promoter region and that loss of MYST3 histone acetyltransferase (HAT) activity resulted in loss of ER α expression in breast cancer cells. The role of MYST in ER α regulation coupled with our increasing understanding of a role for oestrogen signalling in haematopoietic stem cell maintenance might explain the increased incidence of t(8;16) in female patients observed by Kayser et al 1 . and others.…”

“…In considering the report by Kayser et al 1 ,. as well as those that came before, several relevant conclusions can be effectively drawn.…”

“…Acute myeloid leukaemia (AML) with t(8;16)(p11;p13) is a rare AML subtype involving exon 15 or 16 of the MYST3 gene [K(lysine) acetyltransferase 6A ( KAT6A )] on chromosome 8p11 and exons 3–8 of cAMP response element‐binding protein (CREB)‐binding protein (CREBBP, CBP) on chromosome 16p13. In this issue of BJH , Kayser et al 1 . report the findings of an international collaboration to characterise AML associated with t(8;16)(p11;p13) in a cohort of >50 patients treated with standard intensive induction‐like chemotherapy between 1992 and 2016 and with a median follow‐up of 6·48 years.…”

“…The report by Kayser et al 1 . outlines the findings of a collaborative study between multiple European and USA groups and centres.…”