Pediatric acute myeloid leukemia with t(8;16)(p11;p13), a distinct clinical and biological entity: a collaborative study by the International-Berlin-Frankfurt-Münster AML-study group

Abstract

Key Points• Pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features.• Spontaneous remissions occur in a subset of neonatal t(8;16)(p11;p13) AML cases.In pediatric acute myeloid leukemia (AML), cytogenetic abnormalities are strong indicators of prognosis. Some recurrent cytogenetic abnormalities, such as t(8;16)(p11;p13), are so rare that collaborative studies are required to define their prognostic impact. We collected the clinical characteristics, morphology, and immunophenotypes of 62 pediatric AML patients with t(8;16)(p11;p13) from 18 countries participating in the International Berlin-Frankfurt-Münster (I-BFM) AML study group. We used the AML-BFM cohort diagnosed from 1995-2005 (n 5 543) as a reference cohort. Median age of the pediatric t(8;16)(p11;p13) AML patients was significantly lower (1.2 years). The majority (97%) had M4-M5 French-American-British type, significantly different from the reference cohort. Erythrophagocytosis (70%), leukemia cutis (58%), and disseminated intravascular coagulation (39%) occurred frequently. Strikingly, spontaneous remissions occurred in 7 neonates with t(8;16)(p11;p13), of whom 3 remain in continuous remission. The 5-year overall survival of patients diagnosed after 1993 was 59%, similar to the reference cohort (P 5 .14). Gene expression profiles of t(8;16) (p11;p13) pediatric AML cases clustered close to, but distinct from, MLL-rearranged AML. Highly expressed genes included HOXA11, HOXA10, RET, PERP, and GGA2. In conclusion, pediatric t(8;16)(p11;p13) AML is a rare entity defined by a unique gene expression signature and distinct clinical features in whom spontaneous remissions occur in a subset of neonatal cases. (Blood. 2013;122(15):2704-2713

Acute Myeloid Leukemia with Translocation (8;16)(p11;p13): A Distinct Syndrome– Case Report and Literature Review

“…AML with t(8;16)(p11;p13) has a very unique clinical/pathological picture and a poor prognosis, which has resulted in several proposals for a specific subclassification within the FAB system for this entity. As described above, the striking erythrophagocytosis displayed by blasts in AML with t(8;16)(p11;p13) has been discussed as a distinctive feature numerous times in the literature [2][3][4][5][6][7]9,10,14]. The breakpoint observed in AML with t(8;16) (p11;p13) involves genes that are central to erythropoiesis.…”

“…In the case series by Diab et al of 13 patients with AML with t(8;16)(p11;p13), 7 had blasts which exhibited erythrophagocytosis [2]. Amongst pediatric AML with t(8;16) (p11;p13), as many as 70% of cases reported show erythrophagocytosis [3]. Erythrophagocytosis is a relatively rare finding in other types of AML, so this characteristic should raise concern for t(8;16)(p11;p13) as the culprit mutation.…”

“…These gene products are involved in transcriptional regulation and cell cycle control, and they exhibit histone acetyltransferase activity. MYST3, in particular, serves as a co-activator for RUNX1 [2][3][4]. This AML syndrome is characterized by hemophagocytosis by the blasts, extramedullary disease manifestations, and poor prognosis.…”

“…AML with t(8;16)(p11;p13) is not currently included in this list of recurrent genetic abnormalities [12]. A number of papers have proposed that AML with t(8;16)(p11;p13) constitutes its own unique syndrome based on clinical features and immunophenotype [3,5,7,10,13,14]. Classification of AML with t(8;16)(p11;p13) in the current FAB system often becomes unclear when taking immunohistochemistry into account [2,5,7].…”

The Clinical Utility of Genetic Testing for t(8;16)(p11;p13) in Congenital Acute Myeloid Leukemia

“…Three remain in complete remission during follow-up (ranging from 0.9 to 5 y), whereas 4 patients suffered disease recurrence. 7 Diab et al 8 also reported that an infant (age 2 mo) with t(8;16)(p11;p13) AML had spontaneous regression. These reports showed that some cases of t(8;16)(p11;p13) AML regress spontaneously.…”