Characteristics of acute promyelocytic leukemia M3 – immunophenotype

The first works on the cytochemical characterization of blast cells in acute leukemia appeared in the early 60s. During this period, researchers discovered the possibility of differentiating blast elements in acute leukemia, not only by their morphological, but also by physiological (cytochemistry) features.

The classic cytochemical sign of tumor cells in acute promyelocytic leukemia is a very vivid reaction to myeloperoxidase (MPO), Sudan Black (SBB), and chloroacetate esterase. The first in our country and a very detailed description of these signs is given by A. I. Vorobiev et al. in 1968, the authors presented the results of a cytochemical study of blast cells in 11 patients with acute promyelocytic leukemia.

Tumor cells in acute promyelocytic leukemia (APL) have a fairly characteristic immunophenotype. The expression of CD13 and CD33 antigens and a positive reaction with antibodies to myeloperoxidase are determined. The markers of the early stages of differentiation of granulocyte germ cells CD34 and HLA-DR, which are expressed on blast cells in other AML variants, are usually not detected in acute promyelocytic leukemia.

Almost always, with acute promyelocytic leukemia (APL), a reaction with antibodies to the CD9 antigen is positive, and for other forms this marker is not detected. Unfortunately, these antibodies are rarely included in the diagnostic panel.

Rarely, but sometimes, the expression of monocytoid markers CD11b and CD14 is determined, and no correlation with cytochemical reactions to the monocytoid line (nonspecific esterase) is detected. Also, other monocytoid differentiation markers can sometimes be found, such as CD64, very rarely CD65 or CD117. The CD11a antigen, which is expressed on almost all AML cells, is not detected in ALI.

Studies have been conducted to study the expression of lymphoid markers CD7 and CD2. It turned out that the CD7 antigen is always negative, and the CD2 antigen is in some cases positive. Moreover, some researchers propose to allocate as a separate form that variant of APL, which reveals the expression of CD2. Interestingly, there is an association in expression between CD2 and CD34.

Thus, Italian scientists in the analysis of the immunophenotype of blast cells in 114 patients with PLA identified two groups of patients: both CD34 and CD2 (n = 66) are determined on the blast cells, or expression is not determined (n = 20). Positive expression for CD34 was considered the detection of more than 10% of cells expressing CD34, for CD2 – more than 20%. In 28 patients, heterogeneous expression of these antigens was determined.

When comparing clinical, laboratory, cytogenetic data with the indicated immunophenotype, clear correlations were found. With the positive expression of CD2 and CD34, the number of leukocytes in the opening was higher (11.8 • 109 / l versus 1.8 • 109 / l), the number of platelets is smaller (19.5 • 109 / l and 27.5 • 109 / l, respectively ), the percentage of blast cells in the blood was higher (88 and 18%), the bcr3-type of the PML-RAR transcript was determined more often.

Characteristic was the fact that the significance of the differences remained in these parameters and with the exclusion of the micro-granular variant of the APL. So far, no results have been obtained on the effectiveness of modern therapy for the described immunophenotypic variant of APL, therefore it is difficult to interpret the prognostic significance of this phenomenon.

Several groups of researchers have identified significant differences in survival and the likelihood of recurrence in patients with ALI, if CD56 expression is determined on blast cells. The results of the study of Italian scientists GIMEMA patients with PLD clearly show that the expression of CD56 is a negative prognostic sign. Expression is considered positive if 20% or more of the blast cells express the indicated antigen.

Of 100 patients, 15% identified this marker. No differences were found either by sex, age, or the number of leukocytes and platelets in the debut of the disease, nor by the ICE clinic, hemoglobin and fibrinogen content. The duration of remission and the overall survival of these patients was significantly lower than those for whom no expression of CD56 was detected. Other authors confirm this information: if there is CD56 expression, relapse develops in 71.4% of patients, if not, in 12%, which affects the overall survival and the median duration of remission, respectively. Interestingly, these differences are obtained only for APL or AML with t (8; 21), and with other AML variants they are not detected.

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