How can aberrant B lymphoblasts in B lymphoblastic leukemia (B-ALL) be distinguished from hematogones?

Hematogones are immature B-cell precursors that are found primarily in the bone marrow from which they arise. They are found in greatest abundance in infants and young children and decline with age. They are frequently increased in regenerating bone marrow after chemotherapy or bone marrow transplant, but also can be increased in other inflammatory, hematologic, oncologic, and inflammatory disorders. They are rarely detected in peripheral blood.

It is particularly important to be able to differentiate hematogones from neoplastic B-cell precursors in the diagnosis and monitoring of B-ALL. B-lineage lymphoblasts and hematogones often share immunophenotypic characteristics. Thus, hematogone hyperplasia can be mistaken for B-ALL at diagnosis and regenerating hematogones can be mistaken for minimal residual disease after therapy.

Figure 1A shows normal B-lineage maturation. All hematogones are positive for CD19 (not shown) and show variable expression of CD58. The earliest hematogones are bright for CD9, CD10, and CD38, positive for CD34, dim for CD45, and negative for CD20. As they mature, they gain CD20 and then lose CD10. They lose CD34 and then lose CD9 expression. The intensity of CD45 increases and then the intensity of CD38 decreases.

B lymphoblasts in ALL can be differentiated from hematogones by aberrant expression of at least one, but frequently more than one of these markers. An example is shown in Figure 1B. These aberrancies can include over-expression of an antigen, such as CD10, CD34, or CD58, or under-expression of an antigen, such as CD38 or CD45. There can be aberrant co-expression of markers not typically expressed together, such as CD20 and CD34. Sometimes there is aberrant expression of a non-B-cell marker, such as CD13 or CD33. Often aberrancies are most apparent when viewed in combination on 2-dimensional histograms (see Figure 3). The most helpful of these have been shown to be CD58xCD38 and CD10xCD20.
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Understanding the normal immunophenotype of hematogones and how these can be altered aberrantly in B lymphoblasts can help to distinguish hematogone hyperplasia from B-ALL, which is critically important both at diagnosis and during post-therapy monitoring for minimal residual disease

Further Reading:
�1. McKenna RW, Asplund SL, Kroft SH (2004) Immunophenotypic analysis of hematogones (B-lymphocytes precursors) and neoplastic lymphoblasts by 4-color flow cytometry. Leuk Lymphoma. 45:277-285.
�2. Seegmiller AC, Kroft SH, Karandikar NJ, McKenna RW (2009) Characterization of immunophenotypic aberrancies in 200 cases of B acute lymphoblastic leukemia. Am J Clin Pathol. 132:940-949.
3. Shaver AC, Greig BW, Mosse CA, Seegmiller AC (2015) B-ALL Minimal Residual Disease Flow Cytometry: An Application of a Novel Method for Optimization of a Single-Tube Model. AmJ Clin Pathol. 143:716-724.