Benign B-Cell Precursors (Hematogones) Are the Predominant Lymphoid Population in the Bone Marrow of Preterm Infants

Neonatology ◽  
2004 ◽  
Vol 86 (4) ◽  
pp. 247-253 ◽  
Author(s):  
Lisa M. Rimsza ◽  
Vonda K. Douglas ◽  
Patrick Tighe ◽  
Matthew A. Saxonhouse ◽  
Darlene A. Calhoun ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Preterm Infants ◽  
B Cell Precursors

scholarly journals The influence of a dosage regimen of dexamethasone on detection of normal B-cell precursors in the bone marrow of children with BCP-ALL at the end of induction therapy

2020 ◽  
Vol 19 (1) ◽  
pp. 53-57
Author(s):  
E. V. Mikhailova ◽  
T. Yu. Verzhbitskaya ◽  
J. V. Roumiantseva ◽  
O. I. Illarionova ◽  
A. A. Semchenkova ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
B Cell ◽  
Induction Therapy ◽  
Therapy Group ◽  
Lymphoblastic Leukemia ◽  
Leukemic Cells ◽  
Intermittent Therapy ◽  
Continuous Therapy ◽  
B Cell Precursors

Minimal residual disease (MRD) monitoring by flow cytometry at the end of induction therapy is one of the key ways of a prognosis assessment in patients with acute lymphoblastic leukemia (ALL). In B-cell precursor ALL (BCP–ALL), this method of MRD detection is complicated due to the immunophenotypic similarity between leukemic cells and normal B-cell precursors (BCPs). A decrease in intensity of induction therapy can lead to a more frequent appearance of normal BCPs in the bone marrow, which significantly complicates the MRD monitoring. Aim: to assess the incidence of normal BCPs in bone marrow on the 36th day of induction therapy with two different regimens of glucocorticoid (GC) administration according to ALL-MB 2015 protocol. This study was approved by the Independent Ethical Committee and the Academic Council of Dmitriy Rogachev National Medical Research Center of Pediatric Hematology, Oncology, Immunology Ministry of Healthcare of Russian Federation. The study included 220 patients with BCP-ALL who were randomized to two types of GC-based induction therapy: a continuous administration of dexamethasone (n = 139) and an intermittent regimen with a 1-week dexamethasone therapy stop (n = 81). On the 36th day of induction therapy, MRD and normal BCPs were quantified in bone marrow samples by flow cytometry. On the 36th day of treatment, 43.2% of BCP(+) samples were established in the intermittent-therapy group, and 27.3% in the continuous-therapy group (p = 0.016). Comparison of the BCP level in BCP(+) samples revealed the more equitable distribution of BCPs at different developmental stages in the intermittent-therapy group, meanwhile mainly the immature BCPs in a quantity of less than 0.01% were found in the continuous-therapy group. Reduced-intensity induction therapy for patients with BCP-ALL leads to a noticeable increase of normal BCPs in bone marrow at the end of this treatment stage. A higher rate of BCP(+) bone marrow samples hinder the MRD detection due to the immunophenotypic similarity of BCPs and leukemic cells.

Prognostic Impact of Physiological B-Cell Precursors (hematogones) in the Bone Marrow As Determined by Immunophenotyping in the Post-Transplant Period in Patients with AML

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1406-1406
Author(s):  
Ulrike Bacher ◽  
Maximilian Christopeit ◽  
Anneke Heiland ◽  
Mascha Binder ◽  
Tatjana Zabelina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Risk Group ◽  
Disease Stage ◽  
Prognostic Impact ◽  
Myeloid Malignancies ◽  
Post Transplant ◽  
Significant Difference ◽  
The Mean ◽  
B Cell Precursors

Abstract Abstract 1406 Aiming to improve post-transplant monitoring strategies for patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS), approaches to monitor the minimal residual disease load are at present limited to distinct genetic subgroups, e.g. NPM1mut AML. In the conservative treatment setting, increased levels of physiologic B-cell precursors (>0.01% CD10+/CD19+ cells; “hematogones”) as determined by multiparameter flow cytometry (MFC) in the bone marrow (BM) were suggested to be favorable in AML pts (Chantepie et al., Blood, 2011). We investigated whether the prognostic impact of physiologic B-cell precursors can be confirmed in pts with myeloid malignancies in the transplant context. We quantified CD10+/CD19+ B-cell precursors by MFC in the post-transplant period in 76 pts with AML/MDS who received allogeneic hematopoietic stem cell transplantation (HSCT) at Hamburg University, and performed correlation with survival (41 m/35 f; 18–71 yrs; de novo AML: n=51; s-/t-AML: n=11; MDS: n=13). The majority (n=84, 73%) received reduced intensity conditioning (RIC), mainly based on the FLAMSA regimen. Hematogones were evaluated by MFC on days +30 (d30) and +100 (d100) post-HSCT including the following antibody panel: CD19+, CD10+, CD34+, TdT+. Median levels of CD10+/CD19+ cells were 0,06% on day 30 (mean, 0.25%; range, 0–2.4%) and 1.55% on day 100 (mean, 2.13%; range, 0–12.4%). OS from HSCT did not differ on the basis of the CD10+/CD19+ cells measured on d30 (mean±SD=61±6 weeks, for CD10+/CD19+ cells below the mean of 0.25% vs 74±13 weeks for CD10+/CD19+ cells above the mean, RR=0.73, p=0.685). Estimated 1-year-OS±SE was 63±10% for CD10+/CD19+ cells below the mean of 0.25% versus 71±17% for CD10+/CD19+ cells above the mean, respectively. EFS did not show a significant difference, either. Mean CD10+/CD19+ cells on day 100 associated positively with 1-year-OS. In the group below the mean CD10+/CD19+ cells of 2.13%, 1-year-OS±SE was estimated to be 69±9% (median±SEM=89±10 weeks) which was worse when compared to the group above the mean with a 1-year-OS±SE of 83±15% (median±SEM=96±8 weeks; RR=0.124, p=0.046). The effect of low versus high CD10+/CD19+ cells measured at day 100 on EFS was even more pronounced. 1-year-EFS was significantly worse with 60±10% in the group with lower CD10+CD19+ counts on day 100 versus 95±4% in the group with higher counts (RR=0.095, 95%CI=0.012–0.728, p=0.024). In univariate analysis, disease stage, remission status pre-HSCT, cytogenetic risk group and cGVHD had significant influence on OS and/or EFS. By multivariate analysis, CD10+/CD19+ cells on day 100 remained significantly associated with improved EFS (RR=0.998, p=0.001) but significance of the association with OS was lost (RR=0.145, p=0.07). Other factors significantly associated with superior OS and EFS were occurrence of cGVHD (OS: RR=0.997, p=0.049, EFS: RR=0.996, p=0.001), and low/intermediate cytogenetic risk group (OS: RR=0.995, p=0.005, EFS: RR=0.997, p=0.03). To the best of our knowledge, an association of CD10+/CD19+ cells measured by MFC with survival has not been performed after HSCT in pts with AML and MDS. Our study is the first one showing a favorable prognostic impact of increased CD10+/CD19+ cells 100 days after HSCT. It seems that the level of physiological precursors contributes to the prognostic parameters in patients with myeloid malignancies undergoing HSCT. In more detail, a proportion of more than 2.13% of hematogones at day 100 was associated with improved OS and EFS. The association remained positive in multivariate Cox regression analysis, when other parameters such as pre-transplant permission status, disease stage and cGvHD were included. In conclusion, the hematogones level at day 100 seems to be an independent prognostic parameter which should be further evaluated in pts with myeloid malignancies undergoing HSCT. Considering the experience needed for the determination of leukemia associated immunophenotypes by MFC, or the lack of molecular markers suitable for MRD monitoring in many AML and MDS patients, the introduction of hematogones measurement at defined time points may contribute to the identification of high-risk patients in the transplant context. Disclosures: Bacher: MLL Munich Leukemia Laboratory: Employment. Haferlach:MLL Munich Leukemia Laboratory: Equity Ownership.

scholarly journals A monoclonal antibody that recognizes B cells and B cell precursors in mice.

1981 ◽  
Vol 153 (2) ◽  
pp. 269-279 ◽  
Author(s):  
R L Coffman ◽  
I L Weissman
Keyword(s):  
Monoclonal Antibody ◽  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Plasma Cells ◽  
Bone Marrow Cells ◽  
Cell Lineage ◽  
Hematopoietic Stem ◽  
B Cell Precursors

The monoclonal antibody, RA3-2C2, appears to be specific for cells within the B cell lineage. This antibody does not recognize thymocytes, peripheral T cells, or nonlymphoid hematopoietic cells in the spleen or bone marrow. Nor does it recognize the pluripotent hematopoietic stem cells, the spleen colony-forming unit, All sIg+ B cells and most plasma cells are RA3-2C2+. In addition, approximately 20% of nucleated bone marrow cells are RA3-2C2+ but sIg-. This population contains B cell precursors that can give rise to sIg+ cells within 2 d in vitro.

scholarly journals Contact Between Human Bone Marrow Stromal Cells and B Lymphocytes Enhances Very Late Antigen-4/Vascular Cell Adhesion Molecule-1–Independent Tyrosine Phosphorylation of Focal Adhesion Kinase, Paxillin, and ERK2 in Stromal Cells

Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1626-1635 ◽  
Author(s):  
Lisa J. Jarvis ◽  
Jean E. Maguire ◽  
Tucker W. LeBien
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Tyrosine Phosphorylation ◽  
Stromal Cells ◽  
Stromal Cell ◽  
Late Antigen ◽  
Normal Human ◽  
B Cell Precursors ◽  
Cell Adhesion Molecule 1 ◽  
Human B Cell

Contact with bone marrow stromal cells is crucial for the normal growth and development of B-cell precursors. We have previously shown that human bone marrow stromal cell tyrosine kinase activity can be activated by direct contact with B-lymphoid cells (J Immunol 155:2359, 1995). In the present study, we show that increased tyrosine phosphorylation of focal adhesion kinase, paxillin, and extracellular-related kinase 2 (or p42 MAP kinase) accounted for the major changes occurring in stromal cell tyrosine phosphorylation after 5 to 10 minutes of contact with the RAMOS B-lymphoma cell line. Although adhesion of B-cell precursors to stromal cells is primarily mediated by very late antigen-4 (VLA-4) and vascular cell adhesion molecule-1 (VCAM-1), VLA-4–deficient and adhesion-deficient RAMOS cells were equally capable of stimulating stromal cell tyrosine phosphorylation. Similar changes in the tyrosine phosphorylation pattern of stromal cells were induced by contact with normal human B-cell precursors and several other B-lineage cell lines. After 5 to 30 minutes of contact with stromal cells, no change in protein tyrosine phosphorylation was detected in RAMOS or normal human B-cell precursors removed from stromal cells. Pretreatment of stromal cells with cytochalasin D abrogated contact-mediated enhancement of stromal cell tyrosine phosphorylation, suggesting that an intact cytoskeleton was essential. These results suggest that B-cell contact activates stromal cell signaling cascades that regulate cytoskeletal organization and transcription, independent of the interaction mediated by VLA-4 and VCAM-1.

scholarly journals Differential expression levels of the heat shock protein 27 isoforms in pediatric normal, nonleukemic and common acute lymphoblastic leukemia B- cell precursors

Blood ◽  
1995 ◽  
Vol 85 (2) ◽  
pp. 510-521
Author(s):  
PS Madsen ◽  
P Hokland ◽  
N Clausen ◽  
J Ellegaard ◽  
M Hokland
Keyword(s):  
Signal Transduction ◽  
Molecular Weight ◽  
Bone Marrow ◽  
Acute Lymphoblastic Leukemia ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
B Cell ◽  
Isoelectric Point ◽  
Lymphoblastic Leukemia ◽  
B Cell Precursors

Heat shock protein 27 (hsp27) may function as a regulator of microfilament dynamics and may participate in signal transduction pathways of different cell growth regulators, with the mitogen- activated protein kinase-activated protein (MAPKAP) kinase 2 being a major enzyme responsible for its phosphorylation. Using two-dimensional gel electrophoresis, we have compared the expression levels of two hsp27 isoelectric variants (hsp27 isoforms) M2 (molecular weight, 26 kD; isoelectric point, 6.02) and M3 (molecular weight, 26 kD; isoelectric point, 5.60) in pediatric bone marrow CD19+CD10+B-cell precursors (BCPs) purified from either common acute lymphoblastic leukemia (c-ALL) patients, normal donors, or non-c-ALL patients. Compared with normal BCPs, we found increased hsp27 expressions (M2 isoform) (by a factor 5 to 9 of mean level) in c-ALL as well as in non- c-ALL (nonleukemic) precursors. Though increased phosphorylation of hsp27 (M3 isoform) was observed in BCPs from c-ALL patients at relapse (by a factor 3 of mean level compared with normal BCPs and precursors from c-ALL at diagnosis), which might represent a differential enzymatic activity, this was not distinguishable from that of non-c-ALL patients. Therefore, our studies suggest constitutive differences of hsp27 isoforms between pediatric leukemic BCPs and their relatively low- expressing, immunophenotypically normal bone marrow counterparts. In light of the occasional and possibly transient increase of hsp27 expression during nonleukemic BCP differentiation and the possible role of hsp27 in signal transduction to microfilaments, these differences might be of considerable biologic interest and of importance in future studies of regulated normal or dysregulated leukemic hematopoietic cellular differentiation.

scholarly journals Relationship between T200 antigen expression and stages of B cell differentiation in resurgent hyperplasia of bone marrow

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1165-1172 ◽  
Author(s):  
CW Caldwell ◽  
WP Patterson
Keyword(s):  
Bone Marrow ◽  
Cell Differentiation ◽  
B Cell ◽  
Mononuclear Cells ◽  
Antigen Expression ◽  
B Cell Differentiation ◽  
Cell Surface Antigens ◽  
Cell Hyperplasia ◽  
Quantitative Expression ◽  
B Cell Precursors

Abstract Using monoclonal antibodies (MoAbs) and dual-parameter flow cytometric techniques, bone marrow mononuclear cells (MMC) from patients with resurgent hyperplasia were analyzed for their coexpression of HLe-1 (T200) and antigens normally associated with particular stages of B cell differentiation. The marrow from those with resurgent hyperplasia contained increased numbers of B cell precursors in multiple stages of differentiation compared to controls, thus providing a useful model system for studies of B cell differentiation. These studies indicate that the quantitative expression of T200 is differentiation-related on normal and malignant B cells and B cell precursors. Immature cells express low amounts of T200, while increasing levels of maturity correlated with increasing amounts of the antigen. This study increases the understanding of relationships between B cell surface antigens and T200 and further demonstrates that B cell hyperplasia occurs commonly in association with bone marrow reactive or resurgent processes. The quantitative, rather than only the qualitative, expression of T200 is therefore a useful marker of B cell differentiation in reactive hyperplasia and in further investigation of B cell malignancy.

scholarly journals Culture of human fetal B-cell precursors on bone marrow stroma maintains highly proliferative CD20dim cells

Blood ◽  
1993 ◽  
Vol 81 (5) ◽  
pp. 1170-1178 ◽  
Author(s):  
I Moreau ◽  
V Duvert ◽  
J Banchereau ◽  
S Saeland
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Optimal Growth ◽  
Lymphoid Cells ◽  
Interleukin 7 ◽  
Cd20 Expression ◽  
Cell Layers ◽  
Marrow Stroma ◽  
B Cell Precursors ◽  
Dose Dependent

Growth of human B-cell precursors (BCP) was achieved by plating fetal CD10+ surface-mu (s mu)- cells in liquid medium onto bone marrow- derived fibroblastic stromal cell layers deprived of hematopoietic cells. Proliferation of the fetal BCP was strongly potentiated by the addition of interleukin-7 (IL-7) to the cultures. Cultures included both a stroma-adherent and -nonadherent fraction of lymphoid cells, allowing us to expand the number of input BCP to 13-fold. In the presence of exogenous IL-7, proliferation was dose-dependent relative to the number of stromal cells, demonstrating that soluble IL-7 does not act alone to promote optimal growth. We further showed that the lymphoid cells recovered remain CD10+ sIg- BCP and that most cells expressed the maturation-associated CD20 antigen when IL-7 was added to the cultures. Whereas both freshly isolated CD20- and CD20bright BCP proliferated in the presence of stroma, we observed that high- proliferative capacity CD20dim cells were maintained in the cultures. Finally, CD20dim sorted cells were shown to subsequently acquire high levels of CD20 expression in culture, thus demonstrating a partial maturation sequence. The present culture system thus represents a useful model for studying the regulatory signals in early human B lymphopoiesis.

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