|
|
 Previous Article | Table of Contents | Next Article 
Blood, 15 February 2002, Vol. 99, No. 4, pp. 1356-1363
NEOPLASIA
Frequent mutations in the ligand-binding domain of PML-RAR
after multiple relapses of acute promyelocytic leukemia: analysis for
functional relationship to response to all-trans
retinoic acid and histone deacetylase inhibitors in vitro and
in vivo
Da-Cheng Zhou,
Soon H. Kim,
Wei Ding,
Cynthia Schultz,
Raymond P. Warrell Jr, and
Robert E. Gallagher
From the Departments of Oncology and Pathology,
Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY;
and the Developmental Chemotherapy and Leukemia Services, Department of
Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY.
This study identified missense mutations in the ligand binding
domain of the oncoprotein PML-RAR in 5 of 8 patients with acute
promyelocytic leukemia (APL) with 2 or more relapses and 2 or more
previous courses of all-trans retinoic acid
(RA)-containing therapy. Four mutations were novel (Lys207Asn,
Gly289Arg, Arg294Trp, and Pro407Ser), whereas one had been previously
identified (Arg272Gln; normal RAR1 codon assignment). Five patients
were treated with repeat RA plus phenylbutyrate (PB), a histone
deacetylase inhibitor, and one patient experienced a prolonged clinical
remission. Of the 5 RA + PB-treated patients, 4 had
PML-RAR mutations. The Gly289Arg mutation in the clinical responder
produced the most defective PML-RAR function in the presence of RA
with or without sodium butyrate (NaB) or trichostatin A. Relapse APL
cells from this patient failed to differentiate in response to RA but
partially differentiated in response to NaB alone, which was augmented
by RA. In contrast, NaB alone had no differentiation effect on APL cells from another mutant case (Pro407Ser) but enhanced differentiation induced by RA. These results indicate that PML-RAR mutations occurred with high frequency after multiple RA treatment relapses, indicate that the functional potential of PML-RAR was not correlated with clinical response to RA + PB treatment, and suggest that the
response to RA + PB therapy in one patient was related to the
ability of PB to circumvent the blocked RA-regulated gene response pathway.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
G. Cunha De Santis, M. de Barros Tamarozzi, R. B. Sousa, S. E. Moreno, D. Secco, A. B. Garcia, A. S. G. Lima, L. H. Faccioli, R. P. Falcao, F. Q. Cunha, et al.
Adhesion molecules and differentiation syndrome: phenotypic and functional analysis of the effect of ATRA, As2O3, phenylbutyrate, and G-CSF in acute promyelocytic leukemia
Haematologica,
December 1, 2007;
92(12):
1615 - 1622.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Quere, A. Baudet, B. Cassinat, G. Bertrand, J. Marti, L. Manchon, D. Piquemal, C. Chomienne, and T. Commes
Pharmacogenomic analysis of acute promyelocytic leukemia cells highlights CYP26 cytochrome metabolism in differential all-trans retinoic acid sensitivity
Blood,
May 15, 2007;
109(10):
4450 - 4460.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Ohnuma-Ishikawa, T. Morio, T. Yamada, Y. Sugawara, M. Ono, M. Nagasawa, A. Yasuda, C. Morimoto, K. Ohnuma, N. H. Dang, et al.
Knockdown of XAB2 Enhances All-Trans Retinoic Acid-Induced Cellular Differentiation in All-Trans Retinoic Acid-Sensitive and -Resistant Cancer Cells
Cancer Res.,
February 1, 2007;
67(3):
1019 - 1029.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Liu, M. Guo, Y.-B. Xu, D. Li, Z.-N. Zhou, Y.-L. Wu, Z. Chen, S. C. Kogan, and G.-Q. Chen
Induction of tumor arrest and differentiation with prolonged survival by intermittent hypoxia in a mouse model of acute myeloid leukemia
Blood,
January 15, 2006;
107(2):
698 - 707.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Lo-Coco and E. Ammatuna
The Biology of Acute Promyelocytic Leukemia and Its Impact on Diagnosis and Treatment
Hematology,
January 1, 2006;
2006(1):
156 - 161.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Gleissner, N. Goekbuget, H. Rieder, R. Arnold, S. Schwartz, H. Diedrich, C. Schoch, B. Heinze, C. Fonatsch, C. R. Bartram, et al.
CD10- pre-B acute lymphoblastic leukemia (ALL) is a distinct high-risk subgroup of adult ALL associated with a high frequency of MLL aberrations: results of the German Multicenter Trials for Adult ALL (GMALL)
Blood,
December 15, 2005;
106(13):
4054 - 4056.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Altucci, A. Rossin, O. Hirsch, A. Nebbioso, D. Vitoux, E. Wilhelm, F. Guidez, M. De Simone, E. M. Schiavone, D. Grimwade, et al.
Rexinoid-Triggered Differentiation and Tumor-Selective Apoptosis of Acute Myeloid Leukemia by Protein Kinase A-Mediated Desubordination of Retinoid X Receptor
Cancer Res.,
October 1, 2005;
65(19):
8754 - 8765.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Di Croce
Chromatin modifying activity of leukaemia associated fusion proteins
Hum. Mol. Genet.,
April 15, 2005;
14(suppl_1):
R77 - R84.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Cote, S. McNamara, D. Brambilla, A. Bianchini, G. Rizzo, S. V. del Rincon, F. Grignani, C. Nervi, and W. H. Miller Jr
Expression of SMRT{beta} promotes ligand-induced activation of mutated and wild-type retinoid receptors
Blood,
December 15, 2004;
104(13):
4226 - 4235.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Witcher, H. Y. Shiu, Q. Guo, and W. H. Miller Jr
Combination of retinoic acid and tumor necrosis factor overcomes the maturation block in a variety of retinoic acid-resistant acute promyelocytic leukemia cells
Blood,
November 15, 2004;
104(10):
3335 - 3342.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Gurrieri, K. Nafa, T. Merghoub, R. Bernardi, P. Capodieci, A. Biondi, S. Nimer, D. Douer, C. Cordon-Cardo, R. Gallagher, et al.
Mutations of the PML tumor suppressor gene in acute promyelocytic leukemia
Blood,
March 15, 2004;
103(6):
2358 - 2362.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. J. Ley, P. J. Minx, M. J. Walter, R. E. Ries, H. Sun, M. McLellan, J. F. DiPersio, D. C. Link, M. H. Tomasson, T. A. Graubert, et al.
A pilot study of high-throughput, sequence-based mutational profiling of primary human acute myeloid leukemia cell genomes
PNAS,
November 25, 2003;
100(24):
14275 - 14280.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. K. Mann, A. Rephaeli, A. L. Colosimo, Z. Diaz, A. Nudelman, I. Levovich, Y. Jing, S. Waxman, and W. H. Miller Jr.
A Retinoid/Butyric Acid Prodrug Overcomes Retinoic Acid Resistance in Leukemias by Induction of Apoptosis
Mol. Cancer Res.,
October 1, 2003;
1(12):
903 - 912.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Cote, A. Rosenauer, A. Bianchini, K. Seiter, J. Vandewiele, C. Nervi, and W. H. Miller Jr
Response to histone deacetylase inhibition of novel PML/RARalpha mutants detected in retinoic acid-resistant APL cells
Blood,
September 18, 2002;
100(7):
2586 - 2596.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
