Abnormalities of Chromosome Band 8p11 in Leukemia: Two Clinical Syndromes Can Be Distinguished on the Basis of MOZ Involvement

Abstract

Two distinct leukemia syndromes are associated with abnormalities of chromosome band 8p11. First, a myeloproliferative disorder with features characteristic of both chronic myeloid leukemia and non-Hodgkin's lymphoma and second, an acute myeloid leukemia (AML) with French-American-British (FAB) M4/5 morphology and prominent erythrophagocytosis. The two syndromes are exemplified by a t(8; 13)(p11; q12) and a t(8; 16)(p11; p13), respectively, but cytogenetic variants of both have been described. Recently, the t(8; 16) has been cloned and shown to fuse the MOZ gene at 8p11 to the CBP gene at 16p13. We have used fluorescence in situ hybridization (FISH), Southern blotting, and reverse transcriptase-polymerase chain reaction (RT-PCR) to refine the 8p11 breakpoint in three cases with t(8; 13)(p11; q12) and in a single case of AML-M5 with a clinical picture apparently identical to that found in patients with a t(8; 16), but characterized by an inv(8)(p11q13). FISH analysis was performed with several 8p11 CEPH yeast artificial chromosome (YAC) clones. YAC 782H11 was centromeric to the one case with t(8; 13) tested, but was telomeric to the inv(8). YAC 847B12 was telomeric to both the t(8; 13) and the inv(8), whereas YAC 829D12 was centromeric to the t(8; 13), but split by the inv(8). Southern blotting and PCR of YAC 829D12 showed that it contained the MOZ gene. A 900-bp MOZ fragment encompassing the published t(8; 16) breakpoint was amplified by PCR from normal peripheral blood leukocyte cDNA and used to probe Southern blots of patient DNA. A rearrangement was detected in the case with inv(8), but not in any of the three cases with t(8; 13). Southern blotting with a CBP probe and RT-PCR with MOZ and CBP primers suggested that the inv(8) does not result in a cryptic MOZ-CBP fusion. It is likely, therefore, that MOZ is fused to a novel gene at 8q13 in this case. We conclude that the t(8; 13) breakpoint is flanked by YACs 782H11 and 847B12 and is at least 1 Mb telomeric to MOZ. MOZ is involved, however, in a new variant of the t(8; 16).

Two cases of inv(8)(p11q13) in AML with erythrophagocytosis: a new cytogenetic variant

“…A novel gene, MOZ, has been cloned at the 8p11 breakpoint in the t(8;16) (Borrow et al, 1996). MOZ was rearranged in our patient 1, but was not rearranged in three other patients with the t(8;13) (Aguiar et al, 1997). The t(8;16) partner gene at 16p13 is the CREBbinding protein (CBP) (Borrow et al, 1996), but CBP was not rearranged in our patient 1 (Aguiar et al, 1997), suggesting the presence of a novel partner gene at 8q13.…”

Constitutional trisomy 8p11.21‐q11.21 mosaicism: a germline alteration predisposing to myeloid leukaemia

“…Within the minimally gained region, the MOZ‐YBF2/SAS3‐SAS2‐TIP60 protein 3 ( MYST3 ) gene, also known as monocytic leukaemia zinc finger protein ( MOZ ), is a promising candidate gene due to its involvement in the translocations t(8;16)(p11;p13) and t(8;22)(p11;q13), as well as in the inversion inv(8)(p11q13), which are all recurrent chromosomal abnormalities found in both de novo and therapy‐related AML (Aguiar et al , 1997; Chaffanet et al , 2000; Kitabayashi et al , 2001; Imamura et al , 2003). Patients with the translocation t(8;16)(p11;q13) had features similar to those seen in JMML, such as myelomonocytic blasts, frequent extramedullary involvement and poor outcome (Borrow et al , 1996; Bernasconi et al , 2000; Sun & Wu, 2001; Haferlach et al , 2009).…”

Enhanced Cisplatin Response with Histone Acetyl Transferase Inhibitor, Anacardic Acid, in Malignant Pleural Mesothelioma Cell Line

“…31,32 Ayrıca, akut miyeloid lösemide HAT genlerinin translokasyonu görülmektedir. 33,34 Bunlara ek olarak kolorektal, gastrik, meme ve pankreatik kanserde ise HAT aktivitesi olan p300 molekülünü kodlayan gende mutasyonların olduğu da bilinmektedir. 35,36 Bu güne kadar HDAC inhibitörleri ile ilgili birçok çalışma olmasına rağmen HAT inhibitörleri ile ilgili literatürde çok az bilgi vardır.…”