Therapy-related acute myeloid leukemia with t(2;11)(q37;q23) after treatment for osteosarcoma

MLL-SEPTIN gene fusions in hematological malignancies

“…Interestingly, the majority (65%) of pediatric patients with MLL rearrangements have ALL , which led us to hypothesize that the SEPT6 domains of the MLL-SEPT6 chimeric protein might be involved in myeloblastic leukemogenesis in children. Another interesting finding is the association of MLL-SEPT2 fusion and therapy related leukemia, with all the four published MLL-SEPT2 cases being t-AML or t-MDS patients (Table 1) (Cerveira et al, 2006;van Binsbergen et al, 2007;Snijder et al, 2008;Bielorai et al, 2010). The prognostic impact of MLL-SEPTIN fusions remains unknown due to the small number of cases reported in each subgroup and the lack of availability of follow up data in most cases (Table 1).…”

“…DSBs can also result from exposure to drugs targeting topoisomerase II and there is strong evidence supporting the hypothesis that topoisomerase II inhibitor related leukemia is closely associated with the presence of MLL gene rearrangements (Pui and Relling, 2000). Interestingly, all four patients with the MLL-SEPT2 fusion developed t-MDS/ t-AML after chemotherapy for a previous neoplasia with topoisomerase II inhibitors (Cerveira et al, 2006;van Binsbergen et al, 2007;Snijder et al, 2008;Bielorai et al, 2010). The mapping of two sequences with 94.4% homology with the topoisomerase II consensus cleavage site to MLL intron 7 and to SEPT2 intron 2 in one of the MLL-SEPT2 patients provides support to a link between topoisomerase II inhibitor therapy and the origin of the MLL-SEPT2 fusion gene (Cerveira et al, 2006).…”

“…Subsequently, a second MLL-SEPT2 fusion variant involving the fusion between MLL exon 9 and SEPT2 exon 3 (type II fusion transcript) was identified in a patient with t-AML of the M2 FAB subtype (van Binsbergen et al, 2007), and a third MLL-SEPT2 alternative fusion variant (MLL exon 11 with SEPT2 exon 3 -type III fusion transcript) was uncovered by our group in a case of therapy-related myelodysplastic syndrome (t-MDS) (Cerveira et al, 2008b;Snijder et al, 2008). Recently, a fourth case of the MLL-SEPT2 fusion (with the type III variant) was described in a patient that developed a t-AML of the M5 FAB subtype 26 months after treatment for osteosarcoma (Bielorai et al, 2010). Interestingly, although the breakpoints in the MLL BCR can be quite diverse involving distinct exons, in SEPT2 they always occur in intron 2, leading to the formation of a fusion protein where the N-terminus of MLL is always fused to almost the entire open reading frame of SEPT2, except for the first three amino acids (Figure 1).…”

The incidence and distribution characteristics of MLL rearrangements in Chinese acute myeloid leukemia patients by multiplex nested RT-PCR

“…In addition, as reposrted in previous literature, MLL gene rearrangement is likely to occur after other cancer treatment-related leukemia. Application of etoposide, epirubicin Star, cyclophosphamide and other drugs can precipitate treatment-induced leukemia, particularly M4 and M5 type [18][19][20][21]. The prognosis of treatment-related leukemia is poor, and attention should be paid to screening for MLL rearrangements.…”

Pediatric Aleukemic Leukemia Cutis

“…35,37 Isolated cases have been described in the setting of Philadelphia chromosome-positive biphenotypic leukemias. 23,44,45 Therapy-related leukemias because of topoisomerase II inhibitors tend to present sooner after therapy than those because of alkylating agents and have monocytic differentiation, commonly because of the MLL rearrangement, fitting with our patient's presentation. 36 Otsubo et al 26 reported the development of an acute promyelocytic leukemia after ALC in association with NPM-RARA fusion transcript in a child.…”