Identification of Basogranulin (BB1) as a Novel Immunohistochemical Marker of Basophils in Normal Bone Marrow and Patients With Myeloproliferative Disorders

Abstract

In myeloproliferative disorders (MPDs), basophils typically increase in number in the bone marrow (BM) and blood. In chronic myeloid leukemia (CML), basophilia is a diagnostic and prognostic variable. However, no reliable approach for routine detection and enumeration of basophils in BM sections is available. We applied the antibasogranulin antibody BB1 on paraffin-embedded BM sections in 21 control samples (normal BM), 45 patients with CML, 9 with chronic idiopathic myelofibrosis, 11 with polycythemia vera, 19 with essential thrombocythemia, and 7 with indolent systemic mastocytosis. As assessed by immunostaining of serial BM sections, BB1+ cells coexpressed myeloperoxidase, histidine decarboxylase, and leukosialin but did not express B- or T-cell-restricted antigens. BB1+ BM cells were found to be highly elevated in patients with CML compared with normal BM or other MPDs, with maximum counts found in accelerated phase CML (median, 160 cells/mm(2)). In summary, BB1 (basogranulin) is a new immunohistochemical basophil marker that should allow quantification of basophils in CML at diagnosis and during therapy.

NADPH Oxidase–Independent Formation of Extracellular DNA Traps by Basophils

“…We stained basophils with anti-basogranulin Ab (23,24) and PI. Using confocal microscopy, we could demonstrate that basogranulin, a granule protein specifically expressed by basophils, is released following activation of these cells, colocalizing with the extracellular DNA (Fig.…”

The underestimated role of basophils in Ph+ chronic myeloid leukaemia

“…However, a number of useful immunohistochemical basophil stains that work in paraffin‐embedded BM section material, have been developed. These markers include the 2D7 antigen and the BB1 antigen, also known as basogranulin 48, 49. In addition, immature BM basophils express KIT and tryptase 50.…”

“…In addition, immature BM basophils express KIT and tryptase 50. It has also been described that basophils in CML can be detected and enumerated by 2D7 or BB1 staining and that the numbers of 2D7 +  and BB1 +  cells (basophils) correlate with the phase of CML 48, 49. However, both antibodies may also react with immature eosinophils in the leukaemic BM (P. Valent and H.‐P.…”

“…Basophils may also increase in number in Ph‐negative MPN, especially in patients with primary myelofibrosis (PMF) 49, 83. In most of these patients, basophilia is mild contrasting the excessive basophilia seen in CML.…”

Standards and Impact of Hematopathology in Myelodysplastic Syndromes (MDS)

“…For basophil evaluation and counting, 2D7 and BB1 (basogranulin) are recommended antigens ( Figure 1E) [23,24] while eosinophils can be visualized using an antibody against eosinophil major basic protein (EMBP) ( Figure 1F). Whereas a slight or moderate increase of eosinophils is often seen in reactive and neoplastic disease states, constant basophilia is uncommon in reactive states and thus regarded as a potential indicator for the presence of a myeloid neoplasm.…”