Paediatric acute myeloid leukaemia with the t(7;12)(q36;p13) rearrangement: a review of the biological and clinical management aspects

Abstract

The presence of chromosomal abnormalities is one of the most important criteria for leukaemia diagnosis and management. Infant leukaemia is a rare disease that affects children in their first year of life. It has been estimated that approximately one third of infants with acute myeloid leukaemia harbour the t(7;12)(q36;p13) rearrangement in their leukaemic blasts. However, the WHO classification of acute myeloid leukaemia does not yet include the t(7;12) as a separate entity among the different genetic subtypes, although the presence of this chromosomal abnormality has been associated with an extremely poor clinical outcome. Currently, there is no consensus treatment for t(7;12) leukaemia patients. However, with the inferior outcome with the standard induction therapy, stem cell transplantation may offer a better chance for disease control. A better insight into the chromosome biology of this entity might shed some light into the pathogenic mechanisms arising from this chromosomal translocation, that at present are not fully understood. Further work is needed to improve our understanding of the molecular and genetic basis of this disorder. This will hopefully open some grounds for possible tailored treatment for this subset of very young patients with inferior disease outcome. This review aims at highlighting the cytogenetic features that characterise the t(7;12) leukaemias for a better detection of the abnormality in the diagnostic setting. We also review treatment and clinical outcome in the cases reported to date.

Nuclear Repositioning of the Non-Translocated <b><i>HLXB9</i></b> Allele in the Leukaemia Cell Line GDM-1 Harbouring a t(6;7)(q23;q36)

“…The correct maintenance of the higherorder chromatin structure is crucial for cellular health, and its alteration is an emerging factor in human cancer, including leukaemia [Bártová et al, 2000;Ballabio et al, 2009;Tosi et al, 2015]. Over the past decade or so, the observations obtained using microscope imaging and analysis of FISH data were further supported by the introduction of the chromosome conformation capture technique [Dekker et al, 2002] and its variants, such as the high-throughput chromosome conformation capture [Lieberman-Aiden et al, 2009].…”

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

“…7,8 In 2006, von Bergh et al 9 reported that the translocation t(7;12) (q36;p13) was identified in about 30% of infant AML and associated with a poor outcome. [11][12][13][14][15] It involves heterogeneous breakpoints at 12p13 of the ETV6 gene (previously named TEL) and at 7q36, in which the MNX1 gene (motor neuron and pancreas homeo-box1, previously named HLXB9) has been identified as the partner gene. The translocation has not yet been included in the WHO classification for AML.…”

“…It was suggested that accurate identification of t(7;12) would improve risk evaluation and therapy stratification for childhood AML. 11,12,[15][16][17] In the t(7;12)(q36;p13), the breakpoints on chromosome 12 are consistently between exons 1 and 3 at the 5 0 end of ETV6, whereas the breakpoints on chromosome 7 are more heterogeneous affecting band q36 in regions proximal to MNX1. 10 The translocation is often cryptic and most reliably detected using FISH.…”

“…The translocation has not yet been included in the WHO classification for AML. 15 However, the fusion transcript is only identified in approximately 50% of the cases. [11][12][13][14][15] It involves heterogeneous breakpoints at 12p13 of the ETV6 gene (previously named TEL) and at 7q36, in which the MNX1 gene (motor neuron and pancreas homeo-box1, previously named HLXB9) has been identified as the partner gene.…”

Hematological Malignancies. Lymphocytic Leukaemia

“…Ведущее место среди опухолей детского возраста отводится острым лейкозам (30%), при этом 4/5 всех случаев острых лейкозов у детей приходится на острый лимфобластный лейкоз, 1/5 -на острый миелобластный лейкоз [9] (рис. 6).…”