PMID- 22390313
OWN - NLM
STAT- MEDLINE
DCOM- 20120719
LR  - 20211203
IS  - 1756-8722 (Electronic)
IS  - 1756-8722 (Linking)
VI  - 5
DP  - 2012 Mar 5
TI  - Cytogenetic and molecular predictors of response in patients with myeloid 
      malignancies without del[5q] treated with lenalidomide.
PG  - 4
LID - 10.1186/1756-8722-5-4 [doi]
AB  - BACKGROUND: While lenalidomide (LEN) shows high efficacy in myelodysplastic 
      syndromes (MDS) with del[5q], responses can be also seen in patients presenting 
      without del[5q]. We hypothesized that improved detection of chromosomal 
      abnormalities with new karyotyping tools may better predict response to LEN. 
      DESIGN AND METHODS: We have studied clinical, molecular and cytogenetic features 
      of 42 patients with MDS, myeloproliferative neoplasms (MPN), MDS/MPN overlap 
      syndromes and secondary acute myeloid leukemia (sAML) without del[5q] by 
      metaphase cytogenetics (MC) who underwent therapy with LEN. RESULTS: Fluorescence 
      in situ hybridization (FISH) or single nucleotide polymorphism array 
      (SNP-A)-based karyotyping marginally increased the diagnostic yield over MC, 
      detecting 2/42 (4.8%) additional cases with del[5q], one of whom were responded 
      to LEN. Responses were more often observed in patients with a normal karyotype by 
      MC (60% vs abnormal MC; 17%, p = .08) and those with gain of chromosome 8 
      material by either of all 3 karyotyping methods (83% vs all other chromosomal 
      abnormalities; 44% p = .11). However, 5 out of those 6 patients received combined 
      LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material 
      respond well to AZA. The addition of FISH or SNP-A did not improve the predictive 
      value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, 
      ASXL1, TP53, RAS, IDH1/2, and DNMT-3A was performed on 21 of 41 patients, and 
      revealed 13 mutations in 11 patients, but did not show any molecular markers of 
      responsiveness to LEN. CONCLUSIONS: Normal karyotype and gain of chromosome 8 
      material was predictive of response to LEN in non-del[5q] patients with myeloid 
      malignancies.
FAU - Sugimoto, Yuka
AU  - Sugimoto Y
AD  - Department of Translational Hematology and Oncology Research, Cleveland Clinic 
      Taussig Cancer Institute, Cleveland, OH, USA.
FAU - Sekeres, Mikkael A
AU  - Sekeres MA
FAU - Makishima, Hideki
AU  - Makishima H
FAU - Traina, Fabiola
AU  - Traina F
FAU - Visconte, Valeria
AU  - Visconte V
FAU - Jankowska, Anna
AU  - Jankowska A
FAU - Jerez, Andres
AU  - Jerez A
FAU - Szpurka, Hadrian
AU  - Szpurka H
FAU - O'Keefe, Christine L
AU  - O'Keefe CL
FAU - Guinta, Kathryn
AU  - Guinta K
FAU - Afable, Manuel
AU  - Afable M
FAU - Tiu, Ramon
AU  - Tiu R
FAU - McGraw, Kathy L
AU  - McGraw KL
FAU - List, Alan F
AU  - List AF
FAU - Maciejewski, Jaroslaw
AU  - Maciejewski J
LA  - eng
GR  - K24 HL-077522/HL/NHLBI NIH HHS/United States
GR  - R01HL-082983/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20120305
PL  - England
TA  - J Hematol Oncol
JT  - Journal of hematology & oncology
JID - 101468937
RN  - 0 (DNMT3A protein, human)
RN  - 4Z8R6ORS6L (Thalidomide)
RN  - EC 2.1.1.37 (DNA Methyltransferase 3A)
RN  - F0P408N6V4 (Lenalidomide)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Chromosome Aberrations
MH  - *Chromosome Deletion
MH  - Chromosomes, Human, Pair 5/*genetics
MH  - DNA Methyltransferase 3A
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Karyotyping
MH  - Lenalidomide
MH  - Leukemia, Myeloid, Acute/drug therapy/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Mutation/genetics
MH  - Myelodysplastic Syndromes/drug therapy/*genetics/pathology
MH  - Myeloproliferative Disorders/drug therapy/*genetics/pathology
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Prognosis
MH  - Thalidomide/*analogs & derivatives/therapeutic use
PMC - PMC3323440
EDAT- 2012/03/07 06:00
MHDA- 2012/07/20 06:00
PMCR- 2012/03/05
CRDT- 2012/03/07 06:00
PHST- 2012/01/11 00:00 [received]
PHST- 2012/03/05 00:00 [accepted]
PHST- 2012/03/07 06:00 [entrez]
PHST- 2012/03/07 06:00 [pubmed]
PHST- 2012/07/20 06:00 [medline]
PHST- 2012/03/05 00:00 [pmc-release]
AID - 1756-8722-5-4 [pii]
AID - 10.1186/1756-8722-5-4 [doi]
PST - epublish
SO  - J Hematol Oncol. 2012 Mar 5;5:4. doi: 10.1186/1756-8722-5-4.