Abstract
Biphenotypic acute leukemia (BAL) represents a rare type of acute leukemia (AL) with the reported incidence of 4.0–8.5% and poor response to treatment. In adult BAL, poor prognosis is related to unfavorable cytogenetics and P-glycoprotein over-expression (
Legrand et al, Br J Haematol 1998;100:147–55
). It is presumed that better knowledge of its biological features could improve the classification and clinical management of this rare type of acute leukemia. Due to paucity of data regarding biological parameters of BAL, in this study we have analyzed the rearrangements of immunoglobulin heavy chain (IgH) and T-cell receptor g (TCRg) genes, expression of cyclin A1 (CycA1) and HOXA9 genes as well as in vitro growth of 10 de novo BALs and compared them with 15 AML and 15 ALL, respectively. The diagnosis of BAL was established according to EGIL criteria. BAL represented 4.3% of adult and 3.0% of pediatric patients with de novo AL referred to our institution during the 1999–2003 period. Of 10 BALs studied, lymphoid BAL (L2) was identified in 3 children, myeloid BAL (M1 and M5) was identified in 3 adults and one child, BAL of undifferentiated cytomorphology (AUL) in 2 adult patients, whereas one 5-month-old child presented with two separate blast cell populations (L1+M5b, bilineal BAL). With regard to immunophenotype, the group of BAL patients was also heterogeneous: 8/10 expressed the combination of myeloid and B-lymphoid antigens and 2/10 expressed myeloid and T-lymphoid antigens. The majority of BAL expressed CD34 (89%). Cytogenetic analysis was obtained in 7 BAL patients, of whom 3 showed chromosome 11 aberrations and 1 had Ph+ chromosome. Our results indicate that IgH and TCRγ gene rearrangements correlated well with lymphoid BAL morphology. Interestingly, the majority of lymphoid BAL showed oligoclonal amplification of antigen-receptor genes, indicating the coexistence of several malignant clones at the time of presentation. The expression of CycA1 correlated well with myeloid and undifferentiated BAL morphology. In contrast, the expression of HOXA9, a marker associated with myeloid cell lineage, showed no strong correlation with BAL morphology. BAL showed almost equal in vitro growth in three different serum-free culture conditions (no addition of GF, addition of IL-7 and FL or GM-CSF and FL), indicating that their growth was less dependent on the addition of exogenous GFs. Finally, in vitro growth of blasts during a 7-day culture showed autonomous cell growth in 3/10 AML and 3/8 myeloid BAL samples tested, but not in any of the AL with lymphoid features. Finally, further studies are needed to confirm these findings and to extend research to a broader spectrum of cell markers aiming to give a better definition of this rare group of AL.Author notes
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2005, The American Society of Hematology
2005
