Invited reviewHematogones: An overview
Section snippets
History of hematogones
Hematogones (B-lymphocyte precursors) were first described in 1937 by Peter Vogel as “lymphoid-appearing cells” in bone marrow aspirates from children [1]. The term hematogones comes from the Latin term “hematogonia” meaning “blood-maker” and describes cells of uncertain significance.
For several decades their origin and function were unknown. Several terms have been used to describe these immature, lymphoid-appearing bone marrow cells, including marrow precursor cells [2], post-therapeutic stem
Morphologic features
Hematogones (HGs) are lymphoid-appearing cells. A bone marrow trephine biopsy study of HGs-rich specimens showed that the most immature cells were diffusely dispersed within the bone marrow without significant clustering [31].
Examination of bone marrow smears allowed a better appreciation of their cytological characteristics [32]. Although the diameter varied from 10 to 20 μ, these morphologically distinct cells characteristically exhibit highly condensed, uniform nuclear chromatin and scant
Immunophenotypic features
With the arrival of multi-parametric FC and peroxidase staining, HGs were identified as bone marrow B-cells precursors. HGs are non reactive with Sudan black B, myeloperoxidase and non-specific esterase stains [6], [8]. Flow cytometry has become the most useful tools for characterizing HGs [7], [17], [29]. Several studies have described the different stage of HG development [8], [9], [42]. Fig. 2 depicts the phenotypic characteristics of the three stages of HGs.
The most immature recognizable
HG localization
HG detection by morphologic examination in peripheral blood has been performed in neonates [5], [19], [28] and blood from umbilical cord blood [3], [8], [34]. They are usually identified in the majority of bone marrow samples using a 4-color flow cytometry assay [31], [43]. They can also be identified using sensitive flow cytometry in the peripheral blood in 65% of adults with various clinical conditions. Only mature HGs (stage 3) were found, comprising 0.01–1.3% of WBCs (median 0.06%, mean
Minimal residual disease detection in ALL
The most important application of HG's phenotype knowledge is to distinguish HGs from minimal residual disease in patients treated for B-ALL. Currently, the most reliable method to study MRD in ALL is flow cytometric analysis of leukemia-associated immunophenotypes (LAiP) (aberrant phenotypes expressed in leukemic cells but not in normal bone marrow cells). Aberrant immunophenotypes are found in more than 90% of patients with newly diagnosed ALL and that would allow the detection of MRD at the
Conclusion
HGs are normal B-cell precursors first described more than 70 years ago. Their recognition by flow cytometry has led to the study of HGs in several pathological conditions. However in healthy individuals, the normal number of HGs in the bone marrow remains unknown. The main characteristic of the HG phenotype is continuous and discrete antigen maturation patterns. There is not a unique phenotype but rather a dynamic evolution of antigens that distinguishes HGs. The identification of HGs is
Acknowledgments
Contributors: S.P.C and O.R designed the study. S.P.C, E.C, V.S, A.C.G, O.R wrote the paper. E.C and V.S provided pictures and flow cytometry graphs. All authors critically revised the manuscript and approved the final version of the manuscript.
The authors declare no competing financial interests.
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