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

Clonal chromosome abnormalities in Philadelphia negative cells could concern chronic myeloid leukaemia patients treated by tyrosine kinase inhibitors. The European Leukemia Net distinguishes -7/del(7q) abnormalities as a 9warning9. However, the prognosis of clonal chromosome abnormalities in Philadelphia negative cells, and specifically those of -7/del(7q), on clinical outcomes is unclear and based on case-reports showing morphological dysplasia and increased risk of acute myeloid leukaemia, suggesting the coexistence of chronic myeloid leukemia and high-risk myelodysplastic syndrome. We aim to determine whether the impact of -7/del(7q) clonal chromosome abnormalities in Philadelphia negative cells on the clinical outcome is different from the others type of abnormalities, and we argue for an underlying associated high-risk myelodysplastic syndrome. From 102 chronic myeloid leukemia patients with clonal chromosome abnormalities in Philadelphia negative cells with more than median of 6 years follow-up, patients with -7/del(7q) present more frequently signs of dysplasia, lower cumulative incidence of MR4.5 and often need further treatment lines, thus impacting EFS and PFS. 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 NGS mutations patterns could not clearly explain the underlying high-risk disease. We hereby confirm the pejorative prognostic value of -7/del(7q) CCA/Ph- and suggest that myelodysplastic features constitute a warning signal for optimal tyrosine kinase inhibitor response.