PMID- 19445675
OWN - NLM
STAT- MEDLINE
DCOM- 20090707
LR  - 20211020
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 9
DP  - 2009 May 15
TI  - Both SEPT2 and MLL are down-regulated in MLL-SEPT2 therapy-related myeloid 
      neoplasia.
PG  - 147
LID - 10.1186/1471-2407-9-147 [doi]
AB  - BACKGROUND: A relevant role of septins in leukemogenesis has been uncovered by 
      their involvement as fusion partners in MLL-related leukemia. Recently, we have 
      established the MLL-SEPT2 gene fusion as the molecular abnormality subjacent to 
      the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In 
      this work we quantified MLL and SEPT2 gene expression in 58 acute myeloid 
      leukemia patients selected to represent the major AML genetic subgroups, as well 
      as in all three cases of MLL-SEPT2-associated myeloid neoplasms so far described 
      in the literature. METHODS: Cytogenetics, fluorescence in situ hybridization 
      (FISH) and molecular studies (RT-PCR, qRT-PCR and qMSP) were used to characterize 
      58 acute myeloid leukemia patients (AML) at diagnosis selected to represent the 
      major AML genetic subgroups: CBFB-MYH11 (n = 13), PML-RARA (n = 12); 
      RUNX1-RUNX1T1 (n = 12), normal karyotype (n = 11), and MLL gene fusions other 
      than MLL-SEPT2 (n = 10). We also studied all three MLL-SEPT2 myeloid neoplasia 
      cases reported in the literature, namely two AML patients and a t-MDS patient. 
      RESULTS: When compared with normal controls, we found a 12.8-fold reduction of 
      wild-type SEPT2 and MLL-SEPT2 combined expression in cases with the MLL-SEPT2 
      gene fusion (p = 0.007), which is accompanied by a 12.4-fold down-regulation of 
      wild-type MLL and MLL-SEPT2 combined expression (p = 0.028). The down-regulation 
      of SEPT2 in MLL-SEPT2 myeloid neoplasias was statistically significant when 
      compared with all other leukemia genetic subgroups (including those with other 
      MLL gene fusions). In addition, MLL expression was also down-regulated in the 
      group of MLL fusions other than MLL-SEPT2, when compared with the normal control 
      group (p = 0.023) CONCLUSION: We found a significant down-regulation of both 
      SEPT2 and MLL in MLL-SEPT2 myeloid neoplasias. In addition, we also found that 
      MLL is under-expressed in AML patients with MLL fusions other than MLL-SEPT2.
FAU - Cerveira, Nuno
AU  - Cerveira N
AD  - Department of Genetics, Portuguese Oncology Institute, Porto, Portugal. 
      nscerveira@gmail.com
FAU - Santos, Joana
AU  - Santos J
FAU - Bizarro, Susana
AU  - Bizarro S
FAU - Costa, Vera
AU  - Costa V
FAU - Ribeiro, Franclim R
AU  - Ribeiro FR
FAU - Lisboa, Susana
AU  - Lisboa S
FAU - Correia, Cecilia
AU  - Correia C
FAU - Torres, Lurdes
AU  - Torres L
FAU - Vieira, Joana
AU  - Vieira J
FAU - Snijder, Simone
AU  - Snijder S
FAU - Mariz, Jose M
AU  - Mariz JM
FAU - Norton, Lucilia
AU  - Norton L
FAU - Mellink, Clemens H
AU  - Mellink CH
FAU - Buijs, Arjan
AU  - Buijs A
FAU - Teixeira, Manuel R
AU  - Teixeira MR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090515
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 0 (KMT2A protein, human)
RN  - 149025-06-9 (Myeloid-Lymphoid Leukemia Protein)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 3.1.3.2 (Phosphoric Monoester Hydrolases)
SB  - IM
MH  - *Down-Regulation
MH  - Gene Expression Regulation, Neoplastic
MH  - Histone-Lysine N-Methyltransferase
MH  - Humans
MH  - Leukemia, Myeloid, Acute/*genetics/metabolism/therapy
MH  - Myeloid-Lymphoid Leukemia Protein/*genetics/metabolism
MH  - Neoplasms, Second Primary/*genetics/metabolism
MH  - Phosphoric Monoester Hydrolases/*genetics/metabolism
PMC - PMC2689242
EDAT- 2009/05/19 09:00
MHDA- 2009/07/08 09:00
PMCR- 2009/05/15
CRDT- 2009/05/19 09:00
PHST- 2008/12/03 00:00 [received]
PHST- 2009/05/15 00:00 [accepted]
PHST- 2009/05/19 09:00 [entrez]
PHST- 2009/05/19 09:00 [pubmed]
PHST- 2009/07/08 09:00 [medline]
PHST- 2009/05/15 00:00 [pmc-release]
AID - 1471-2407-9-147 [pii]
AID - 10.1186/1471-2407-9-147 [doi]
PST - epublish
SO  - BMC Cancer. 2009 May 15;9:147. doi: 10.1186/1471-2407-9-147.