A complex t(1;22;11)(q44;q13;q23) translocation causing MLL‐p300 fusion gene in therapy‐related acute myeloid leukemia

Abstract

The p300 protein shows a striking homology with cyclic-AMP-response-element-binding-protein binding protein (CBP) and both proteins form a family of DNA-binding transcriptional coactivators/histone acetyltransferases. The authors, herein, report a therapy-related acute myeloid leukemia with MLL-p300 fusion gene. Spectral karyotyping clarified that chromosome 11 is involved in complex t(1;22;11)(q44;q13;q23), and is fused to the chromosome 22, and direct sequencing revealed the fusion of exon 8 of MLL and exon 15 of p300 in this case. This is only the second reported case of leukemia with an MLL-p300 fusion gene, and the other case with MLL-p300 was also a therapy-related leukemia. Considering that the MLL-CBP fusion gene is also found almost exclusively in therapy-related leukemia, the association of MLL-p300 and MLL-CBP with therapy-related leukemia rather than de novo leukemia is thereby suggested.

Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma

“…While this evidence implicates CBP/EP300 as tumor suppressors, evidence also supports their oncogenic activity. Rare human leukemias have been found with oncogenic fusion proteins containing either CBP or EP300, and these oncogenic fusion proteins require the activity of CBP or EP300 ( Murati et al, 2007 ; Ohnishi et al, 2008 ; Yung et al, 2011 ; Wang et al, 2011 ). Genetic ablation and pharmacological inhibition of CBP/EP300 in leukemic cell lines and primary patient samples also support the oncogenic role of CBP and EP300 ( Picaud et al, 2015 ; Giotopoulos et al, 2015 ).…”

“…Cyclic AMP response element binding protein (CREB)-binding protein (CBP) and E1A interacting protein of 300 kDa (EP300) are highly homologous bromodomain-containing transcriptional co-activators that regulate a number of important cellular events through their acetyltransferase activity ( Goodman and Smolik, 2000 ). Genetic studies in mice and surveys of human cancer mutations and translocations have implicated CBP/EP300 in cancer, but the role of the bromodomain in the normal and pathological function of CBP/EP300 has not been extensively studied ( Kung et al, 2000 ; Murati et al, 2007 ; Ohnishi et al, 2008 ; Pasqualucci et al, 2011 ; Peifer et al, 2012 ). Given the importance of these genes in cancer development, CBP/EP300 bromodomain inhibition may represent an important therapeutic strategy to reprogram oncogenic signaling pathways in human malignancies.…”

A case of Acute Lymphoblastic Leukemia with rare t(11;22)(q23;q13)

“…Currently there are only three reported cases in the literature with t(11;22)(q23;q13), unlike our case all having secondary acute myeloid leukemia with prior therapy of topoisomerase II inhibitor (table 1). Moreover, rearrangement of the MLL gene and MLL-EP300 fusion gene were demonstrated in those three cases (Ida et al, 1997;Ohnishi et al, 2008;Duhoux et al, 2011). The clinical presentation of our case is quit different from these three cases.…”

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.…”