title: Chromosomal abnormalities in transformed Ph-negative myeloproliferative neoplasms are associated to the transformation subtype and independent of JAK2 and the TET2 mutations.
abstract: Evolution to myelofibrosis (MF), acute myeloid leukemia or myelodysplastic syndrome (AML/MDS) may occur over time in myeloproliferative neoplasms (MPN) patients most likely due to the acquisition of additional mutations. The Groupe Francophone de cytogenetique hematologique (GFCH) has collected and reviewed 82 patients with transformation of MPN (66 AML/MDS and 16 MF). JAK2V617F and TET2 mutations were searched for in 40 and 32 patients, respectively. Significantly more -7/del(7q) (P = 0.004) and -5/del(5q) (P = 0.03) were found in AML/MDS with a higher incidence of dup1q (P = 0.01) in MF. Some specific chromosomal abnormalities occurred together, for example -5/del(5q) and -17/del(17p) (P = 0.0007). In multivariate analysis, two factors were independently associated with an inferior overall survival (OS); AML/MDS transformation (P < 0.0001) and -5/del(5q) abnormality (P = 0.02). Although both giving rise to loss of 7q, der(1;7) differed from other 7q deletions in terms of distribution (lower frequency of AML/MDS, P = 0.02), association with chromosomal abnormalities (absence of -5/del(5q), P = 0.003; increased del(20q), P = 0.05), and longer OS (P = 0.0007). We detected 24/40 (60%) JAK2V617F and 8/25 (32%) TET2 mutations in samples following transformation, ranging from wild-type to mutated forms of both genes. The mutated and wild-type forms of the genes were not found to be associated with a specific chromosomal abnormality. There was no evidence that JAK2 or TET2 mutations were associated with the type of MPN transformation, whereas the type of cytogenetic abnormalities were strongly linked, perhaps indicating that they play a specific role in the transformation process.
authors.affiliation: Hématologie biologique, Hôpital Pitié-Salpêtrière, APHP, Paris, France. florence.nguyen-khac@psl.aphp.fr
authors.forename: Florence
authors.initials: F
authors.lastname: Nguyen-Khac
authors.forename: Claude
authors.initials: C
authors.lastname: Lesty
authors.forename: Virginie
authors.initials: V
authors.lastname: Eclache
authors.forename: Lucile
authors.initials: L
authors.lastname: Couronné
authors.forename: Olivier
authors.initials: O
authors.lastname: Kosmider
authors.forename: Joris
authors.initials: J
authors.lastname: Andrieux
authors.forename: Marie-Agnes
authors.initials: MA
authors.lastname: Collonge-Rame
authors.forename: Dominique
authors.initials: D
authors.lastname: Penther
authors.forename: Marina
authors.initials: M
authors.lastname: Lafage
authors.forename: Chrystele
authors.initials: C
authors.lastname: Bilhou-Nabera
authors.forename: Elise
authors.initials: E
authors.lastname: Chapiro
authors.forename: Marie-Joelle
authors.initials: MJ
authors.lastname: Mozziconacci
authors.forename: Francine
authors.initials: F
authors.lastname: Mugneret
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gachard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Nadal
authors.forename: Eric
authors.initials: E
authors.lastname: Lippert
authors.forename: Stephanie
authors.initials: S
authors.lastname: Struski
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.forename: Christine
authors.initials: C
authors.lastname: Cabrol
authors.forename: Olivier A
authors.initials: OA
authors.lastname: Bernard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics*; D049308:Dioxygenases; D005260:Female; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D054438:Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D049308:Dioxygenases; C541081:TET2 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2