Chromosomal abnormalities in transformed Ph‐negative myeloproliferative neoplasms are associated to the transformation subtype and independent of JAK2 and the TET2 mutations

• DOI: 10.1002/gcc.20802
• Publication Date: 2010-07-13T19:49:34Z
• Authors: Florence Nguyen‐Khac; Claude Lesty; Virginie Eclache; Lucile Couronné; Olivier Kosmider; Joris Andrieux; Marie‐Agnes Collo...; Dominique Penther; Marina Lafage; Chrystele Bilhou‐...; Elise Chapiro; Marie‐Joelle Mozz...; Francine Mugneret; Nathalie Gachard; Nathalie Nadal; Eric Lippert; Stephanie Struski; Nicole Dastugue; Christine Cabrol; Olivier A. Bernard
• Keywords: Adult; Aged, 80 and over; Chromosome Aberrations; Male; 0303 health sciences; DNA Mutational Analysis; Janus Kinase 2; Middle Aged; Prognosis; Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative; Dioxygenases; 3. Good health; DNA-Binding Proteins; Survival Rate; Young Adult; 03 medical and health sciences; Cell Transformation, Neoplastic; Proto-Oncogene Proteins; Mutation; Humans; Female; Aged

AbstractEvolution 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. © 2010 Wiley‐Liss, Inc.