Immunophenotype of adult and childhood acute promyelocytic leukaemia: correlation with morphology, type of PML gene breakpoint and clinical outcome. A cooperative Italian study on 196 cases

Abstract

Summary. Acute promyelocytic leukaemia (APL), characterized by a specific PML-RARa fusion gene resulting from translocation t(15;17) and by a high response rate to differentiation therapy with all-trans retinoic acid, presents clinical (varying WBC counts, age and treatment outcome), morphological (hypergranular M3 and hypogranular M3V) and molecular (three isoforms of PML breakpoint) heterogeneity.We correlated leukaemic immunophenotype with these aspects in 196 molecularly confirmed APLs (63 children and 133 adults) in Italy. The bcr3 isoform (P ¼ 0·05) and FAB M3V (P ¼ 0·05) were more frequent in children. We confirmed in APL an immunophenotype characterized by frequent expression of CD13, CD33 and CD9 and rare expression of HLA-DR, CD10, CD7 and CD11b. However, we recognized CD2 in 28%, CD34 in 23% and CD19 in 11% of cases and demonstrated by double labelling that CD34 and CD2 may be co-expressed. CD2, CD34 and CD19 were significantly intercorrelated, and variably associated to other features: CD2 and CD34 with PML bcr3 (P < 0·001 and P < 0·001, respectively) and with M3V (P < 0·001 and P ¼ 0·002), whereas only CD19 was directly correlated with WBC counts and only CD2 positively influenced CR rate (logistic model) and event-free survival (Cox model). We conclude that immunophenotype plays a role in the determination of the biological and clinical heterogeneity of childhood and adult APL.

CD34‐positive acute promyelocytic leukemia is associated with leukocytosis, microgranular/hypogranular morphology, expression of CD2 and bcr3 isoform

“…Factors associated with an inferior prognosis in t(15;17) APL include older age [3,5,7], increased WBC count at presentation [1,5,7,8], and the detection of the PML-RAR␣ translocation prod-in APL. Typical surface markers include CD13, CD33, and CD9 [12][13][14]. Atypical markers, including CD2 and CD34, have been reported [12,15].…”

“…Typical surface markers include CD13, CD33, and CD9 [12][13][14]. Atypical markers, including CD2 and CD34, have been reported [12,15]. Although the clinical relevance of these immunophenotypic markers is not clearly known, several groups have shown that expression of CD2 is associated with microgranular morphology (M3v) [16,17] and the bcr3 PML-RAR␣ isoform [12,18].…”

Increased bone marrow FDG uptake at PET/CT is not a sufficient proof of bone marrow involvement in diffuse large B‐cell lymphoma

“…Their study included 372 lymphoma patients and comprised a subgroup of 155 patients with diffuse large B-cell lymphoma (DLBCL) who underwent both 18 F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) and unilateral bone marrow biopsy (BMB) of the iliac crest. Sensitivity of FDG-PET/CT and BMB were calculated using the combination of the two tests as reference standard.…”

Introducing biological features at diagnosis improves the relapse risk stratification in patients with acute promyelocytic leukemia treated with ATRA and chemotherapy

“…A joint study reported that morphologic variant subtype had, compared to the classic subtype, higher CIR and significant reduced OS [16]. CD34 expression in APL has been associated with hyperleucocytosis, bcr3 isoform, microgranular variant, and CD2 expression [17,18]. In our experience, isolated CD34 expression identified a subgroup with a classic morphology (79%), bcr1 prevalence (53%), higher rate of relapse (37% vs. 13.8% in the negative group, P 5 0.002), higher incidence of differentiation syndrome (55% vs. 12%, P 5 0.03) and lower OS (60% vs 95%, P 5 0.001).…”