Acute myeloid leukemia (AML) with t(7;12)(q36;p13) is associated with infancy and trisomy 19: Data from Nordic Society for Pediatric Hematology and Oncology (NOPHO‐AML) and review of the literature

Abstract

The t(7;12)(q36;p13) (MNX1/ETV6) is not included in the WHO classification but has been described in up to 30% of acute myeloid leukemia (AML) in children <2 years and associated with a poor prognosis. We present the clinical and cytogenetics characteristics of AML cases with t(7;12)(p36;p13). A literature review identified 35 patients with this translocation, published between 2000 and 2015. Outcome data were available in 22 cases. The NOPHO-AML (Nordic Society for Pediatric Hematology and Oncology) database contained 651 patients with AML from 1993 to 2014 and seven (1.1%) had the translocation. The t(7;12) was only present in patients <2 years of age (median age 6 months) but none was diagnosed as newborn. These patients constituted 4.3% of the patients <2 years of age. There was a strong association with trisomy 19 (literature: 86%, NOPHO: 100%) and +8 (literature: 19%, NOPHO: 14%). Seventeen of 22 patients from the literature with t(7;12) and four of seven patients from the NOPHO database suffered from relapse. The patients with t(7;12) had a 3-year event free survival of 24% (literature) vs. 43% (NOPHO) and a 3-year overall survival of 42% (literature) vs. 100% (NOPHO). None of the NOPHO patients was treated with hematopoietic stem cell transplantation (HSCT) in first complete remission. Relapse was frequent but the salvage rate using HSCT was high. We conclude that t(7;12)(q36;13) is a unique subgroup of childhood AML with presentation before 2 years of age with most cases being associated with +19.

Cytogenetics of Pediatric Acute Myeloid Leukemia: A Review of the Current Knowledge

“…The rare subtle (often cryptic translocation) t(7;12)(q36;p13) presents with a breakpoint 5′ of ETV6 and a variable breakpoint of proximal 7q (upstream) to MNX1 (7q36.3) (for a review, see Espersen et al, 2018 [ 53 ]). It induces ectopic expression of the MNX1 ( HLXB9) homeobox transcription factor with the blockade of differentiation and senescence in hematopoietic progenitors and stem cells.…”

“…However, due to the wide variability of 7q breakpoints, the existence of deletions on the derivative 7q, three-way translocations and cryptic insertions, and the choice of accurate FISH probes is crucial [ 53 , 104 , 105 ]. To date, t(7;12)(q36;p13)/ ETV6-MNX1 has only been described in infants (under 2 years old) with an incidence of 4.3% in infants and 1.1% in pediatric AML, as reported in a recent review [ 53 ]. ACAs are present in 86% of cases, and all cases with ACAs had trisomy 19 [ 53 ].…”

“…To date, t(7;12)(q36;p13)/ ETV6-MNX1 has only been described in infants (under 2 years old) with an incidence of 4.3% in infants and 1.1% in pediatric AML, as reported in a recent review [ 53 ]. ACAs are present in 86% of cases, and all cases with ACAs had trisomy 19 [ 53 ]. In the literature, a high rate of relapse has been reported (77%); however, the salvage rate using HSCT is high [ 53 ].…”

Infant Acute Myeloid Leukemia: A Unique Clinical and Biological Entity

“…In t(7;12)(q36;p13) ETV6 is joined to the regulatory sequences and first exons of the HLXB9 homeobox gene (currently called MNX1), which acts as a transcription factor. This fusion induces overexpression of HLXB9, interferes with normal hematopoietic differentiation and impacts cell maturation [36,[51][52][53].…”

“…This rare translocation, often reported with trisomy 19 is associated with a very dismal prognosis [36,[51][52][53].…”