The immunophenotype of blast transformation of chronic myelogenous leukemia: A high frequency of mixed lineage phenotype in "lymphoid" blasts and a comparison of morphologic, immunophenotypic, and molecular findings

Immunophenotypic studies have a limited role in the diagnosis of chronic my elogenous leukemia (CML) but are increasingly being used in CML blast trans formation (BT). Determination of the cell lineage of CML blasts is clinical ly important because patients with lymphoid blast transformation have a bet ter response to chemotherapy and longer survival than those with other line ages. We studied the morphologic, cytochemical, immunophenotypic, cytogenet ic, and molecular features of 20 patients with Philadelphia chromosome-posi tive CML and more than 10% blast cells in peripheral blood or bone marrow. The blasts were morphologically heterogeneous. CD33 was expressed in 19 cas es (95%), followed by CD13 (85%), CD11c (80%), CD36 (60%), CD117 (40%), and CD15 (30%). Seven cases (35%) had a precursor-B lymphoid immunophenotype, and 13 (65%) had a predominantly myeloid immunophenotype. Of the former gro up, of which only one had a pure lymphoid phenotype, terminal deoxynucleoti dyl transferase (TdT) and CD19 were expressed in 100%, CD10 in 85.7%, and C D20 in 14.3%. Of the latter group, all 13 expressed from 3 to 6 myeloid ant igens, with 46.2% myeloperoxidase positive and 69.2% CD61 positive. No case s were interpreted as T lineage, but the T-cell antigens CD3, CD4, CD5, and CD7 were expressed in 5.0, 40.0, 5.3. and 30.0% of all cases, respectively . In most cases, the immunophenotype of the CML blasts could not be predict ed from their morphologic features. Polymerase chain reaction showed that 8 0.0% of the lymphoid group and 37.5% of the myeloid group had immunoglobuli n heavy-chain gene rearrangements. The frequent lineage infidelity of the b last cells in CML BT seems to be related to the stem cell origin of this di sorder. Such lineage infidelity, however, makes classification of many case s difficult and the significance of and criteria for biphenotypic blast cri sis of CML is yet to be determined.