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

Abstract

Biphenotypic acute leukemia (BAL) is a rare, difficult to diagnose entity. Its identification is important for risk stratification in acute leukemia (AL). The scoring proposal of the European Group for the Classification of Acute Leukemia (EGIL) is useful for this purpose, but its performance against objective benchmarks is unclear. Using the EGIL system, we identified 23 (3.4%) BAL from among 676 newly diagnosed AL patients. Mixed, small and large blast cells predominated, with FAB M2 and L1 constituting the majority. All patients were positive for myeloid (M) markers and either B cell (B) (17 or 74%) or T cell (T) (8 or 34%) markers with two exceptional patients demonstrating trilineage phenotype. Six (50%) of studied M-B cases were positive for both IGH and TCR. In six (26%) patients myeloid lineage commitment was also demonstrable by electron cytochemistry. Abnormal findings were present in 19 (83%) patients by cytogenetics/FISH/molecular analysis as follows: t(9;22) (17%); MLL gene rearrangement (26%); deletion(6q) (13%); 12p11.2 (9%); numerical abnormalities (13%), and three (13%) new, previously unreported translocations t(X;6)(p22.3;q21); t(2;6)(q37;p21.3); and t(8;14)(p21;q32). In conclusion, the EGIL criteria for BAL appear robust when compared against molecular techniques that, if applied routinely, could aid in detecting BAL and help in risk stratification.

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

“…34 The second most frequent genetic lesion in MPAL are translocations involving MLL gene, with the most common partner gene being AF4 on chromosome 4 band q21. 35 This tends to occur more commonly in children and is more frequent in infancy. 36 These cases also tend to present with a dimorphic blast population and the lymphoblasts have a CD19-positive, CD10-negative, B-precursor immunophenotype and are frequently positive for CD15.…”

“…37 The frequency of biphenotypic acute leukemia seems to be similar in all age groups. Owaidah et al 35 found that out of 676 cases of both adult and pediatric acute leukemia patients, 23 cases (3.4%) were diagnosed as biphenotypic by EGIL criteria. In all, 11 patients were aged 14 years or less and the other 12 cases were classified as adults.…”

“…In all, 11 patients were aged 14 years or less and the other 12 cases were classified as adults. 35 Killick et al 34 studied 20 de novo cases of biphenotypic leukemia using EGIL criteria; 8 patients were under the age of 15, whereas 12 were over 15 years of age.…”

“…1 Early on, using variable diagnostic criteria, the reported prevalence of acute leukemia with a mixed phenotype ranged from 2 to 20% of all acute leukemias; however, more recent studies using EGIL criteria show a frequency of 2-5%. 35 Using a panel proposed by EGIL, a recent study that evaluated the immunophenotype of 325 adult leukemias found that 1.8% were biphenotypic. 37 The frequency of biphenotypic acute leukemia seems to be similar in all age groups.…”

“…The prognosis of MPAL patients with MLL rearrangement is poor. 35 If the blasts lack the above-mentioned genetic abnormalities, MPAL cases are categorized by the lineage of the blasts. Thus, there are three other less-specific categories, which include B/myeloid, not otherwise specified, T/myeloid, not otherwise specified, and other rare types of MPAL listed under MPAL, not otherwise specified.…”