Biologic heterogeneity in Philadelphia chromosome-positive acute leukemia with myeloid morphology: the Eastern Cooperative Oncology Group experience

Abstract

Evaluable karyotypes were available in 776 of 1148 adult patients who were entered on acute myeloid leukemia (AML) treatment protocols of the Eastern Cooperative Oncology Group. Among these, we found seven patients (0.9%) with t(9;22)(q34;q11), the Philadelphia (Ph) chromosome, in bone marrow metaphases. All fulfilled the FAB criteria for AML (three M0, two M1, two M2), although one patient presented with an additional, distinct lymphoid blast cell population. Chromosomal aberrations in addition to the Ph chromosome were seen in four patients (including two cases of monosomy 7). Molecular analysis by polymerase chain reaction in four patients tested revealed variable BCR/ABL transcript forms (ela2, b2a2, b3a2, b2a3+e1a2). By immunophenotyping, all seven patients were myeloid based on the overall antigen expression pattern. However, all but one demonstrated lymphoid-associated antigens on the myeloid blast cells. The six evaluable patients failed to respond to treatment with a standard anthracycline/cytosine arabinoside-containing regimen. We conclude that the incidence of the Ph chromosome in AML is very low. Although both genotypically and phenotypically heterogenous, Ph chromosome-positive AML, represents a clinically distinct entity with poor outcome.

Antigen expression patterns reflecting genotype of acute leukemias

“…236,237 Cases with de novo AML carrying BCR/ABL are most often positive for CD13, CD18 and HLA-DR. Expression of B cellrelated antigens is frequent.…”

“…Expression of B cellrelated antigens is frequent. 170,236,238 Potentially important information regarding the pathogenesis of BCR/ABL pos leukemia comes from case reports. A patient with Philadelphia chromosome (Ph)-positive acute mixed-lineage leukemia that expressed both major and minor BCR/ABL mRNA transcripts has been described.…”

A novel translocation t(3;21)(p21;q22) in acute myelogenous leukemia preceding a late-appearing Philadelphia chromosome

“…5 This immaturity is usually reflected immunophenotypically; many cases exhibit markers of poorly differentiated AML (CD11b þ , low expression of CD65 and absence of CD14 and CD15), usually coexpressed with lymphoid-associated markers (CD10, CD19, CD20, Cd7 and terminal deoxynucleotidyl transferase (TdT)), suggesting leukemic transformation of a primitive myeloid/lymphoid stem cell. 4 In this report, the blasts were initially negative for CD19, but subsequently showed partial coexpression of CD19 upon demonstration of the Ph chromosome. Second, Ph-positive AML cases have higher initial WBC counts and poorer responses to conventional induction chemotherapy than Ph-negative AML cases.…”

“…4 Whether cases of Ph-positive AML represent a distinct clinical entity or rather undiagnosed cases of CML in blast phase has been controversial, although most authors contend that Ph-positive AML is a bona fide entity. 4,5 Several observations support this notion. First, although most FAB subtypes may present with the Ph chromosome, these cases tend to demonstrate a high degree of immaturity and present as M0, M1 or M2 subtypes.…”

De Novo Philadelphia Positive Acute Myeloid Leukemia with Extensive Basophilia: A Diagnostic Dilemma

“…Ph ? AML constitute \1 % of newly diagnosed cases of AML [9,10] and presence of basophilia in such cases has rarely been reported. Igarashi et al [6] reported a case with similar findings, where blasts harboring minor bcr-abl chimeric mRNA showed basophilic differentiation.…”