Characterization of Immunophenotypic Aberrancies in 200 Cases of B Acute Lymphoblastic Leukemia
Characterization of Immunophenotypic Aberrancies in 200 Cases of B Acute Lymphoblastic Leukemia
Morphologic distinction of leukemic lymphoblasts in B acute lymphoblastic leukemia (B-ALL) from their nonneoplastic counterparts in bone marrow (hematogones) can be difficult. Thus, the presence of aberrant antigen expression detectable by flow cytometry may be critical for diagnosis of B-ALL and detection of minimal residual disease. The current study examined the immunophenotype of B-lineage leukemic lymphoblasts in 200 consecutive, unique, pretreatment patient specimens. We found that all cases of B-ALL exhibited multiple immunophenotypic aberrancies by which they can be distinguished from hematogones. The most frequent aberrancies were uniform or a spectrum of expression of terminal deoxynucleotidyl transferase and CD34, underexpression of CD45, overexpression of CD10, underexpression of CD38, and underexpression of CD20. Asynchronous coexpression of CD34 and CD20 was also frequently observed. Of the 200 cases, 86.5% expressed myeloid-associated antigens, and 19.0% expressed 3 or more. Of 200 cases, 9.0% aberrantly expressed T cell–associated antigens. There were significant differences in antigen-expression patterns between adult and pediatric B-ALL. Specific aberrancies correlate with recurrent cytogenetic abnormalities in B-ALL.
B acute lymphoblastic leukemia (B-ALL) is a neoplasm of immature B cells (lymphoblasts) that are committed to the B-cell developmental lineage. The nonneoplastic counterparts of leukemic B lymphoblasts, normal bone marrow B-cell precursors, are commonly referred to as hematogones. Hematogones may be abundant in healthy infants and children and are frequently increased in patients with cytopenias of various etiologies. They may even be detectable in minute numbers in the blood by flow cytometry. Furthermore, hematogones are often increased in the bone marrow of patients who have received chemotherapy or stem cell transplant. Hematogones, especially if present in large numbers, may confound the diagnosis of B-ALL in 1 of 2 ways: (1) Hematogone hyperplasia in a background of cytopenias may be mistaken for B-ALL at initial diagnosis. (2) Increased hematogones in a patient treated for B-ALL may be mistaken for residual or recurrent leukemia. Consequently, the ability to distinguish hematogones from leukemic lymphoblasts on immunophenotypic or morphologic grounds is critical for accurate diagnosis.
The immunophenotype of hematogones has been well characterized in several large studies. Other studies have characterized immunophenotypic aberrancies found in leukemic lymphoblasts that help to distinguish them from developing hematogones. The current study extends these findings by reporting the expression patterns of a more complete set (31) of cell-surface antigens, including not only B-lymphoid antigens but also myeloid, T-lymphoid, and NK-cell markers in one of the largest cohorts (200 patients) of newly diagnosed pretreatment B-ALL examined to date. We demonstrate that there are discernible immunophenotypic aberrancies in every case of B-ALL. Furthermore, for the first time, we show that there are differences in the immunophenotypic patterns of children and adults with this disease, some of which can be explained by differences in the distribution of recurrent cytogenetic abnormalities in these age groups. We also describe several novel immunophenotype-karyotype correlations. All of these findings are considered in light of the most recent classification scheme for acute leukemia.
Abstract and Introduction
Abstract
Morphologic distinction of leukemic lymphoblasts in B acute lymphoblastic leukemia (B-ALL) from their nonneoplastic counterparts in bone marrow (hematogones) can be difficult. Thus, the presence of aberrant antigen expression detectable by flow cytometry may be critical for diagnosis of B-ALL and detection of minimal residual disease. The current study examined the immunophenotype of B-lineage leukemic lymphoblasts in 200 consecutive, unique, pretreatment patient specimens. We found that all cases of B-ALL exhibited multiple immunophenotypic aberrancies by which they can be distinguished from hematogones. The most frequent aberrancies were uniform or a spectrum of expression of terminal deoxynucleotidyl transferase and CD34, underexpression of CD45, overexpression of CD10, underexpression of CD38, and underexpression of CD20. Asynchronous coexpression of CD34 and CD20 was also frequently observed. Of the 200 cases, 86.5% expressed myeloid-associated antigens, and 19.0% expressed 3 or more. Of 200 cases, 9.0% aberrantly expressed T cell–associated antigens. There were significant differences in antigen-expression patterns between adult and pediatric B-ALL. Specific aberrancies correlate with recurrent cytogenetic abnormalities in B-ALL.
Introduction
B acute lymphoblastic leukemia (B-ALL) is a neoplasm of immature B cells (lymphoblasts) that are committed to the B-cell developmental lineage. The nonneoplastic counterparts of leukemic B lymphoblasts, normal bone marrow B-cell precursors, are commonly referred to as hematogones. Hematogones may be abundant in healthy infants and children and are frequently increased in patients with cytopenias of various etiologies. They may even be detectable in minute numbers in the blood by flow cytometry. Furthermore, hematogones are often increased in the bone marrow of patients who have received chemotherapy or stem cell transplant. Hematogones, especially if present in large numbers, may confound the diagnosis of B-ALL in 1 of 2 ways: (1) Hematogone hyperplasia in a background of cytopenias may be mistaken for B-ALL at initial diagnosis. (2) Increased hematogones in a patient treated for B-ALL may be mistaken for residual or recurrent leukemia. Consequently, the ability to distinguish hematogones from leukemic lymphoblasts on immunophenotypic or morphologic grounds is critical for accurate diagnosis.
The immunophenotype of hematogones has been well characterized in several large studies. Other studies have characterized immunophenotypic aberrancies found in leukemic lymphoblasts that help to distinguish them from developing hematogones. The current study extends these findings by reporting the expression patterns of a more complete set (31) of cell-surface antigens, including not only B-lymphoid antigens but also myeloid, T-lymphoid, and NK-cell markers in one of the largest cohorts (200 patients) of newly diagnosed pretreatment B-ALL examined to date. We demonstrate that there are discernible immunophenotypic aberrancies in every case of B-ALL. Furthermore, for the first time, we show that there are differences in the immunophenotypic patterns of children and adults with this disease, some of which can be explained by differences in the distribution of recurrent cytogenetic abnormalities in these age groups. We also describe several novel immunophenotype-karyotype correlations. All of these findings are considered in light of the most recent classification scheme for acute leukemia.
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