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 myelogenous leukemia (CML) but are increasingly being used in CML blast transformation (BT). Determination of the cell lineage of CML blasts is clinically important because patients with lymphoid blast transformation have a better response to chemotherapy and longer survival than those with other lineages. We studied the morphologic, cytochemical, immunophenotypic, cytogenetic, and molecular features of 20 patients with Philadelphia chromosome-positive CML and more than 10% blast cells in peripheral blood or bone marrow. The blasts were morphologically heterogeneous. CD33 was expressed in 19 cases (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 group, of which only one had a pure lymphoid phenotype, terminal deoxynucleotidyl transferase (TdT) and CD19 were expressed in 100%, CD10 in 85.7%, and CD20 in 14.3%. Of the latter group, all 13 expressed from 3 to 6 myeloid antigens, with 46.2% myeloperoxidase positive and 69.2% CD61 positive. No cases 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 predicted from their morphologic features. Polymerase chain reaction showed that 80.0% of the lymphoid group and 37.5% of the myeloid group had immunoglobulin heavy-chain gene rearrangements. The frequent lineage infidelity of the blast cells in CML BT seems to be related to the stem cell origin of this disorder. Such lineage infidelity, however, makes classification of many cases difficult and the significance of and criteria for biphenotypic blast crisis of CML is yet to be determined.
Khalidi
H S
HS
Division of Pathology, City of Hope National Medical Center, Duarte, California 91010, USA.
Brynes
R K
RK
Medeiros
L J
LJ
Chang
K L
KL
Slovak
M L
ML
Snyder
D S
DS
Arber
D A
DA
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000276:immunology / Q000473:pathology; D006801:Humans; D016130:Immunophenotyping; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D000951:Antigens, Neoplasm; D012334:RNA, Neoplasm