Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoïesis and a high incidence of P53 mutations - PubMed (original) (raw)
Affiliations
- PMID: 7885035
Comparative Study
Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoïesis and a high incidence of P53 mutations
J L Lai et al. Leukemia. 1995 Mar.
Abstract
We looked for correlations between cytogenetic rearrangements leading to 17p deletion and presence of dysgranulopoïesis and p53 mutations in MDS and AML. Forty-nine (4.3%) of the MDS and AML studied cytogenetically at our institution over a period of 11 years had detectable 17p deletion, through monosomy 17 (14 cases) or rearrangements of chromosome 17 (generally unbalanced translocations between 17p and another chromosome) (35 cases). Most of the patients had additional complex cytogenetic findings, and 10 cases were therapy related. In 70% of the patients with 17p deletion, a particular type of dysgranulopoïesis, combining pseudo-Pelger-Huët anomaly and small vacuolated neutrophils was seen in > 5% marrow neutrophils, whereas 69% of the patients had a p53 mutation, generally in a missense mutation involving exons 5 to 8 of the p53 gene. FISH analysis, performed in eight cases, confirmed loss of one P53 allele in all of them. No DNA fragmentation suggesting increased apoptosis was found in marrow samples. Response to chemotherapy was almost uniformly poor and median survival was only 3 months. Analysis of dysgranulopoïesis and p53 mutations were also made in 'control' groups of MDS and AML without 17p deletion. 'Typical' dysgranulopoïesis, combining pseudo-Pelger-Huët anomaly and small vacuolated neutrophils in > 5% marrow neutrophils, was not seen in any of the 47 MDS and AML without 17p deletion analyzed and without p53 mutation (P = 10(-4) with patients having 17p deletion), and was seen in one of five patients without 17p deletion but with a p53 mutation. Only 3.1% of 256 MDS and AML without 17p deletion had a p53 mutation (P = 10(-4) with patients having 17p deletion). These findings suggest that 17p deletion, in MDS and AML, is strongly correlated to the presence of a particular type of dysgranulopoïesis and to a high incidence of p53 mutations, and that MDS and AML with 17p deletion could constitute a new morphological-cytogenetic-molecular entity in myeloid disorders.
Similar articles
- 17p Deletion in acute myeloid leukemia and myelodysplastic syndrome. Analysis of breakpoints and deleted segments by fluorescence in situ.
Soenen V, Preudhomme C, Roumier C, Daudignon A, Laï JL, Fenaux P. Soenen V, et al. Blood. 1998 Feb 1;91(3):1008-15. Blood. 1998. PMID: 9446663 - Therapy-related myelodysplastic syndrome and acute myeloid leukemia with 17p deletion. A report on 25 cases.
Merlat A, Lai JL, Sterkers Y, Demory JL, Bauters F, Preudhomme C, Fenaux P. Merlat A, et al. Leukemia. 1999 Feb;13(2):250-7. doi: 10.1038/sj.leu.2401298. Leukemia. 1999. PMID: 10025899 Clinical Trial. - Acute myeloid leukemia and myelodysplastic syndromes following essential thrombocythemia treated with hydroxyurea: high proportion of cases with 17p deletion.
Sterkers Y, Preudhomme C, Laï JL, Demory JL, Caulier MT, Wattel E, Bordessoule D, Bauters F, Fenaux P. Sterkers Y, et al. Blood. 1998 Jan 15;91(2):616-22. Blood. 1998. PMID: 9427717 - Polysomy 8 defines a clinico-cytogenetic entity representing a subset of myeloid hematologic malignancies associated with a poor prognosis: report on a cohort of 12 patients and review of 105 published cases.
Beyer V, Mühlematter D, Parlier V, Cabrol C, Bougeon-Mamin S, Solenthaler M, Tobler A, Pugin P, Gregor M, Hitz F, Hess U, Chapuis B, Laurencet F, Schanz U, Schmidt PM, van Melle G, Jotterand M. Beyer V, et al. Cancer Genet Cytogenet. 2005 Jul 15;160(2):97-119. doi: 10.1016/j.cancergencyto.2004.12.003. Cancer Genet Cytogenet. 2005. PMID: 15993266 Review. - Alternative genetic pathways and cooperating genetic abnormalities in the pathogenesis of therapy-related myelodysplasia and acute myeloid leukemia.
Pedersen-Bjergaard J, Christiansen DH, Desta F, Andersen MK. Pedersen-Bjergaard J, et al. Leukemia. 2006 Nov;20(11):1943-9. doi: 10.1038/sj.leu.2404381. Epub 2006 Sep 21. Leukemia. 2006. PMID: 16990778 Review.
Cited by
- TP53 Alterations in Myelodysplastic Syndromes and Acute Myeloid Leukemia.
Rahmé R, Braun T, Manfredi JJ, Fenaux P. Rahmé R, et al. Biomedicines. 2023 Apr 11;11(4):1152. doi: 10.3390/biomedicines11041152. Biomedicines. 2023. PMID: 37189770 Free PMC article. Review. - TP53 Mutations in Acute Myeloid Leukemia: Still a Daunting Challenge?
Molica M, Mazzone C, Niscola P, de Fabritiis P. Molica M, et al. Front Oncol. 2021 Feb 8;10:610820. doi: 10.3389/fonc.2020.610820. eCollection 2020. Front Oncol. 2021. PMID: 33628731 Free PMC article. Review. - Acute Myeloid Leukemia and Myelodysplastic Syndromes with TP53 Aberrations - A Distinct Stem Cell Disorder.
Sill H, Zebisch A, Haase D. Sill H, et al. Clin Cancer Res. 2020 Oct 15;26(20):5304-5309. doi: 10.1158/1078-0432.CCR-20-2272. Epub 2020 Aug 14. Clin Cancer Res. 2020. PMID: 32816950 Free PMC article. - Synergistic effects of PRIMA-1Met (APR-246) and 5-azacitidine in _TP53_-mutated myelodysplastic syndromes and acute myeloid leukemia.
Maslah N, Salomao N, Drevon L, Verger E, Partouche N, Ly P, Aubin P, Naoui N, Schlageter MH, Bally C, Miekoutima E, Rahmé R, Lehmann-Che J, Ades L, Fenaux P, Cassinat B, Giraudier S. Maslah N, et al. Haematologica. 2020 Jun;105(6):1539-1551. doi: 10.3324/haematol.2019.218453. Epub 2019 Sep 5. Haematologica. 2020. PMID: 31488557 Free PMC article. - Complex karyotype in de novo acute myeloid leukemia: typical and atypical subtypes differ molecularly and clinically.
Mrózek K, Eisfeld AK, Kohlschmidt J, Carroll AJ, Walker CJ, Nicolet D, Blachly JS, Bill M, Papaioannou D, Wang ES, Uy GL, Kolitz JE, Powell BL, Blum W, Stone RM, Byrd JC, Bloomfield CD. Mrózek K, et al. Leukemia. 2019 Jul;33(7):1620-1634. doi: 10.1038/s41375-019-0390-3. Epub 2019 Feb 8. Leukemia. 2019. PMID: 30737482 Free PMC article.
Publication types
MeSH terms
LinkOut - more resources
Medical
Research Materials
Miscellaneous