CD34+CD38– LEUKEMIC STEM CELL PROFILE CORRELATED WELL WITH THE CYTOGENETIC AND MOLECULAIRE FEATURES IN ACUTE MYELOIDE AND LYMPHOIDE LEUKEMIA AT DIAGNOSIS
A Plesa,1 X Thomas,1 L Campos,2 I Tigaud,3 S Hayette,3 MP Pages,3 F Solly,2 P Flandrin-Gresta,2 Y Chelgoum,4 FE Nicolini,4 L Vila,5 D Treille Ritouet,5 S Morisset,6 Y Bertrand,7 D Guyotat,2 M Michallet,4 C Dumontet5
Background. Acute leukemia is thought to arise from a rare putative ‘leukemic stem cell’(LSC) that is capable of self-renewal and formation of leukemic blasts. CD38 is expressed in acute lymphoblastic leukemia (ALL) and in acute myeloide leukemia (AML) and its prognostic significance is still unknown. Aims. We investigated CD34 and CD38 expression in 93 AML and 73 ALL adults and paediatric patients, and we asked if the frequency of LSC at diagnosis is correlated with specific cytogenetics or molecular events and with the CR and survival. Methods. Diagnosis of leukaemia was based on FAB and WHO classifications. Blasts were identified by CD45dim/SSC characteristics. The “LSC profile”was defined as % of CD34+CD38– in CD34+ gated cells and based on rMFI of CD38 from all CD34+ and CD45dim/SCC gated cells. Results. CD38 was lower in AML-M3 compared to other FAB subtypes. Interestingely, we observed that higher frequency of CD34+CD38– was more associated with secondary AML or AML-MRC (myelodysplasia-related changes), but was similar among the primary AML. We show that reduced relative mean fluorescence of CD38 on CD34+ cells correlate well with the cytogenetics unfavourable and intermediate risk groups in the adults AML (P 0.082 or P 0.014 for variance test). The Ph+ ALL patients showed significant lower CD38 expression than in nonPh+ patients (P 0.0032). Overall survival favored AML and ALL patients with higher CD38 levels. Conclusions. Our results showed that frequency of LSC profile at diagnosis could be predictive for cytogenetics and moleculaire features in acute leukaemia. Screening of CD34+CD38p-value cells is a simple flow cytometry method that might be considered to design a multicolor panel setting in parallel with MRD evaluation. The goal in leukaemia therapy is to eradicate LSC and targeting them after reaching CR should be required. The possibility to detect and characterize LSC should help to reach this goal.