Expression of CD117 and CD11b in Bone Marrow Can Differentiate Acute Promyelocytic Leukemia From Recovering Benign Myeloid Proliferation

Abstract

The morphologic characteristics of bone marrow aspirates from patients recovering from acute agranulocytosis may be closely similar to the pattern observed in cases of acute promyelocytic leukemia (APL). The clinical manifestation also can be ambiguous in a substantial number of cases. The immunophenotypic features of bone marrow from 5 patients recovering from acute agranulocytosis, showing an increase in the percentage of promyelocytes (26%-66%), were compared with the immunophenotype of 31 consecutive patients with APL whose diagnosis was confirmed by PML-RAR alpha gene rearrangement. All markers were similarly expressed, except for CD117 and CD11b. CD117 was positive in 24 (77%) of the APL cases and in none of the acute agranulocytosis cases. On the other hand, CD11b was positive in 5 (100%) of the acute agranulocytosis cases and in only 2 (6%) of the APL cases. Thus, the CD117-CD11b+ phenotype was detected in all patients recovering from agranulocytosis and in only 1 (3%) of 31 APL cases. Therefore, we suggest that the combination of both markers is helpful in the differentiation of APL from recovering benign myeloid proliferation.

Acute promyelocytic leukemia: PML/RARα and the leukemic stem cell

“…In the case of APL, this means to introduce PML/ RARa, RARa/PML plus mutated Flt-3 or c-kit plus bcl-2. [27][28][29] The currently available PML/RARa transgene models do not allow the identification of the LIC in APL and AML. In fact, most of the already established in vivo models of PML/RARa-positive leukemias are based on PML/RARa-transgenes alone [30][31][32][33][34] or in combination with mutated Flt3, a molecule also considered to be crucial in the pathogenesis of AML.…”

“…30 APL blasts are only rarely CD11b positive. 28 A major contribution to answer the question of the LIC and the effect of PML/RARa on myeloid cells derived from the HSCs could be provided by a transduction/transplantation model of PML/RARa-positive leukemia. Such a transduction/transplantation leukemia model not only allows a more refined characterization of subpopulations of the stem cell compartment but also the establishment in an immunocompetent environment.…”

Microgranular and t(11;17)/PLZF‐RARα variants of acute promyelocytic leukemia also present the flow cytometric pattern of CD13, CD34, and CD15 expression characteristic of PML‐RARα gene rearrangement

“…The classical hypergranular and the microgranular (hypogranular) variant are the two morphological subtypes representative of the great majority of APL cases with the t(15;17) translocation [11]. The bone marrow morphology of both subtypes, however, may cause confusion with other diseases in some instances, and problems emerge when morphology is solely used for diagnostic confirmation of APL [12]. In particular, the microgranular variant may be of difficult diagnosis, as it may be confused with other types of AML on morphological grounds [13,14].…”

Asynchronous expression of myeloid antigens in leukemic cells in a PML/RARalpha transgenic mouse model

“…Pharmacological doses of retinoic acid induce the degradation of the PML/RARα fusion protein and disease remission (2). APL has a specific immunophenotypic profile, characterized by the co-expression of the pan-myeloid markers CD13 (with a heterogeneous intensity of expression) and CD33 (homogeneous intensity of expression), and absence or low expression of HLA-DR, CD11a and CD18 (3)(4)(5). APL is mostly CD34 negative and the low expression of this marker has been associated with the microgranular variant and with the expression of the bcr3 PML/RARα isoform (6,7).…”

“…Finally, CD117 is frequently expressed by APL cells, but with variable intensity (5). The study of the immunophenotypic profile of APL has prompted some groups to develop flow cytometry methods for APL diagnosis and minimal residual disease detection (3,4).…”