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Haematologica. 2019 Jun;104(6):1150-1155. doi: 10.3324/haematol.2018.208801. Epub 2018 Dec 20.

Poor prognosis of chromosome 7 clonal aberrations in Philadelphia-negative metaphases and relevance of potential underlying myelodysplastic features in chronic myeloid leukemia.

Author information

1
Laboratoire d'Hématologie, CHU Bordeaux.
2
Institut de Génétique Médicale, Hôpital Jeanne de Flandre, CHU Lille.
3
Centre de Recherche Jean-Pierre Aubert, UMR-S 1172, Université de Lille.
4
Institut d'Hématologie, Centre de Biologie Pathologie Génétique, CHU Lille.
5
Inserm, UMR-S 1172, Lille.
6
Département d'Hématologie, Centre Léon Bérard, Lyon.
7
Service des Maladies du Sang, Hôpital Claude Huriez, CHU Lille.
8
Inserm U1052, Centre de Recherche en Cancérologie, Centre Léon Bérard, Lyon.
9
Laboratoire de Cytogénétique et de Biologie Moléculaire, Service d'Hématologie Biologique - CBPAS, GHS - Hospices Civils de Lyon, Pierre-Bénite Cedex, France.
10
Laboratoire d'Hématologie, Plateau Technique Hématologie-Oncologie, Institut Universitaire du Cancer de Tolouse Oncopole.
11
Laboratoire Central d'Hématologie, Hôpital Robert Debré, Reims.
12
Laboratoire de Génétique Oncologique, Centre de Lutte Contre le Cancer Henri Becquerel, Rouen.
13
Laboratoire d'Hématologie-Cytogénétique, CHU Saint-Etienne, Hôpital Nord, Saint-Etienne Cedex 2.
14
Laboratoire de Génétique Chromosomique et Moléculaire, Plateau Technique de Biologie, CHU de Dijon.
15
Service d'Hématologie Clinique, CHU Estaing, Clermont-Ferrand.
16
Laboratoire de Cytogénétique, CHU Estaing, Clermont-Ferrand.
17
Service Clinique des Maladies du Sang, Hôpital St Louis, Paris.
18
Laboratoire Régional de Cytogénétique Hématologique d'Alsace, CHU de Haute Pierre, Strasbourg Cedex.
19
Laboratoire de Cytogénétique Hématologique, Plateau Technique Hôtel Dieu, Nantes.
20
Laboratoire de Cytogénétique du Centre Hospitalier Valence, Le Chesnay.
21
Service d'Hématologie, Centre Hospitalier Annecy-Genevois, Epagny Metz-Tessy.
22
Unité de Génétique des Hémopathies, Institut de Biologie et Pathologie, CHU Grenoble Alpes, Grenoble Cedex 9.
23
Unité de Génétique Médicale et Cytogénétique, CHU de Nîmes.
24
Laboratoire de Cytogénétique, Hôpital Necker - Enfants Malades, Paris.
25
Laboratoire de Cytogénétique Onco-Hématologie, Hôpital Bretonneau, Tours.
26
Service d'Hématologie Biologique, Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique des Hôpitaux de Paris et Sorbonne Université, Paris.
27
Département d'Hématologie, Institut Bergonié, Bordeaux, France.
28
Institut de Génétique Médicale, Hôpital Jeanne de Flandre, CHU Lille catherine.roche@chru-lille.fr.

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.

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