Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P‐glycoprotein over‐expression

Abstract

Summary. Biphenotypic acute leukaemia (BAL) patients represented 8% of the 287 de novo consecutive adult acute leukaemias (23 BAL, 230 acute myeloid leukaemia (AML) and 34 acute lymphoblastic leukaemia (ALL)) referred to our department during the last 4-year period. Of these 23 BAL patients, 14 patients showed myeloid morphology and nine cases lymphoid morphology according to FAB criteria. There were no differences between lymphoid and myeloid BAL according to clinical and biological presentation and treatment outcome. We confirm the poor prognosis of BAL when compared to AML or ALL seen during the same period of time, in terms of complete remission (47%, 62% and 82% respectively, BAL v AML, NS and BAL v ALL, P ¼ 0·006) and 4-year overall survival (8·1%, 25·8% and 23·8% respectively, BAL v AML, P ¼ 0·05 and BAL v ALL, P ¼ 0·003). Comparing adult BAL patients with AML patients, we found an increase in poor prognostic factors: CD34 þ phenotype (82% v 60% respectively, P ¼ 0·03), unfavourable karyotype (60% v 20%, P < 0·0001) and Pgp over-expression by RT-PCR (0·705 v 0·107, P < 0·0001) and flow cytometry (0·824 v 0·391, P ¼ 0·0001). MRP and LRP were not found to be poor prognostic factors. Comparing BAL patients with ALL patients, we found also an increase in poor prognostic factors: age (51 v 39, P ¼ 0·003) and CD34 þ phenotype (82% v 50%, P ¼ 0·02). We conclude that BAL patients need a more aggressive treatment procedure, including high-dose AraC or the use of Pgp modulators for first-line therapy.

Cytogenetics, molecular and ultrastructural characteristics of biphenotypic acute leukemia identified by the EGIL scoring system

“…Table 1 Primers sequence for molecular analysis (4)(q23)x2,der(4;7) (p10;q10),+t(4;7)(q12;q32), add(6)(p25)x2, +del(6)(q12),add(7)(q11.2),del(7)(p13), +der (7) Our data are similar to previously reported series 9,14,15 ( Table 4). The theory that the cell of origin in BAL is an early hematopoeitic stem cell, is supported by nearly all cases of BAL in our study expressing stem cell marker CD34.…”

“…Few studies have analyzed the diagnostic and prognostic factors, clinical and biological presentation of BAL patients when compared to other ALs. 5,6,[9][10][11] Herein we have utilized morphological, immunophenotypic, cytogenetic and molecular genetic characteristics to assess whether the EGIL scoring system is sufficiently robust, in practice, to define BAL.…”

Mixed-phenotype acute leukemia: historical overview and a new definition

“…Additional abnormalities included deletion of 6q, 5q and 12p. 35 Similar genetic findings were noted by Legrand et al 40 in their study of 23 biphenotypic acute leukemias. These authors also looked at MDR1 gene expression and found that it was higher in patients with biphenotypic acute leukemia than AML using RT-PCR and flow cytometry.…”

“…Similarly, Xue et al 36 found that adult patients with biphenotypic leukemia had a worse overall survival and disease-free survival than those with either AML or ALL. Legrand et al 40 also found that adult patients with biphenotypic acute leukemia had a worse prognosis in terms of achieving complete remission and 4-year overall survival when compared with AML or ALL patients. Pediatric cases of biphenotypic acute leukemia have been found to have better prognosis when compared with adult biphenotypic cases.…”

Expression of IAP-family proteins in adult acute mixed lineage leukemia (AMLL)

“…Anti-apoptosis mechanisms, alterations of tumor suppressor genes, altered immunogenicity, and drug-resistance mechanisms act in combination [39]. AMLL exhibits strong resistance against chemotherapy, resulting in poor patient prognosis [40,41]. In the present study, expression levels of IAPs in AMLL blasts were higher than those in control samples.…”