Cytoplasmic nucleophosmin [cNPM] in acute myeloid leukaemia: Relation to disease characteristics

ABSTRACT

Nucleophosmin/B23 [NPM] is a 38 kDa molecular phosphoprotein involved in ribosome assembly and transport. Findings have revealed a complex scenario of NPM functions and interactions, pointing to proliferative and growth-suppressive roles. NPM appears to be more abundant in tumour cells than in normal cells. The aim of the work was to identify cytoplasmic localization of NPM using bone marrow clot biopsy and correlate it with disease and patient characteristics and the known prognostic factors, induction chemotherapy response and survival after 12 months of follow up. The present work was undertaken on 50 cases of normal karyotype acute myeloid leukaemia classified according to modified FAB system. Bone marrow aspirates were obtained, clotted and a formalin-fixed, paraffin embedded cell block was prepared. Sections were immunostained for NPM. Twenty-six cases [52%] had cytoplasmic positivity [cNPM+] while the remaining 24 cases [48%] had nuclear restricted NPM [cNPM]. cNPM positivity was significantly variable among the different FAB subtypes being the most prevalent among M5 and M2 cases, was associated with high blast and white blood cell count at diagnosis. It was significantly correlated with CD34 negativity, CD14 positivity but not with FLT3 mutations. Clinically no relation between cNPM positivity and age, sex nor extramedullary involvement of the studied patients was proven. The cytoplasmic positivity for NPM was significantly correlated with increased survival and better outcome after cycles of chemotherapy. So it can be regarded as a good prognostic marker. FLT3 positivity affected the survival of the cNPM negative group of patients remarkably, denoting the importance of combining both their statuses to predict outcome of therapy and survival. Our data confirm that cytoplasmic NPM1 immunoreactivity is predictive of NPM1 mutations and can be included in the routine diagnostic and prognostic workup of AML