학술논문
Poor prognosis of chromosome 7 clonal aberrations in Philadelphia-negative metaphases and relevance of potential underlying myelodysplastic features in chronic myeloid leukemia
Document Type
article
Author
Audrey Bidet; Stéphanie Dulucq; Thomas Smol; Alice Marceau-Renaut; Stéphane Morisset; Valérie Coiteux; Marie-Pierre Noël-Walter; Franck-Emmanuel Nicolini; Isabelle Tigaud; Isabelle Luquet; Stéphanie Struski; Baptiste Gaillard; Dominique Penther; Sylvie Tondeur; Nathalie Nadal; Eric Hermet; Lauren Véronèse; Delphine Réa; Carine Gervais; Olivier Theisen; Christine Terré; Pascale Cony-Makhoul; Christine Lefebvre; Jean-Baptiste Gaillard; Isabelle Radford; Anne-Laure Vervaeke; Carole Barin; Elise Chapiro; Florence Nguyen-Khac; Gabriel Etienne; Claude Preudhomme; François Xavier Mahon; Catherine Roche-Lestienne
Source
Haematologica, Vol 104, Iss 6 (2019)
Subject
Language
English
ISSN
0390-6078
1592-8721
1592-8721
Abstract
Clonal chromosome abnormalities in Philadelphia-negative cells could concern chronic myeloid leukemia patients treated by tyrosine kinase inhibitors. The European LeukemiaNet distinguishes -7/del(7q) abnormalities as a “warning”. However, the impact of clonal chromosome abnormalities, and specifically those of -7/del(7q), in Philadelphia-negative cells on clinical outcomes is unclear and based on case-reports showing morphological dysplasia and increased risk of acute myeloid leukemia, suggesting the coexistence of chronic myeloid leukemia and high-risk myelodysplastic syndrome. The aim of this study was to determine whether the impact of -7/del(7q) clonal chromosome abnormalities in Philadelphia-negative cells on the clinical outcome is different from that of other types of abnormalities, and we argue for an underlying associated high-risk myelodysplastic syndrome. Among 102 chronic myeloid leukemia patients with clonal chromosome abnormalities in Philadelphia-negative cells with more than a median of 6 years of follow up, patients with -7/del(7q) more frequently had signs of dysplasia, a lower cumulative incidence of deep molecular response and often needed further treatment lines, with the consequent impact on event-free and progression-free survival. Morphological features of dysplasia are associated with myelodysplastic syndrome/acute myeloid leukemia mutations and compromise the optimal response to tyrosine kinase inhibitors, irrespectively of the type of clonal chromosome abnormalities in Philadelphia-negative cells. However, mutation patterns determined by next-generation sequencing could not clearly explain the underlying high-risk disease. We hereby confirm the pejorative prognostic value of -7/del(7q) clonal chromosome abnormalities in Philadelphia-negative cells and suggest that myelodysplastic features constitute a warning signal that response to tyrosine kinase inhibitors may be less than optimal.