Large Cell Variants of CD5+, CD23− B-Cell Lymphoma/Leukemia

2001 ◽  
Vol 125 (4) ◽  
pp. 513-518
Author(s):  
Cherie H. Dunphy ◽  
Sherrie L. Perkins
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
B Cell ◽  
Cyclin D1 ◽  
Clinical Data ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Cell Leukemia ◽  
Mantle Cell

Abstract Context.—Mantle cell lymphoma (MCL), and its leukemic phase, constitute a well-studied hematologic malignancy with known overall survival, prognostic indicators, morphologic findings at diagnosis and in bone marrow, and known incidence of the bcl-1 immunoglobulin gene rearrangement. Large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype (CD5+, CD23−), including but not limited to blastic MCL, prolymphocytoid MCL, blastic mantle cell leukemia, and prolymphocytic mantle cell leukemia, are not as well characterized. Although blastic MCL is known to be associated with a shorter overall survival than conventional MCL, the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype have not been described as fully as conventional MCL. Objective.—The purpose of the present study was to describe the large cell variants of B-cell lymphoma/leukemia with a mantle cell immunophenotype. Design.—Nineteen cases of large cell variants of CD5+, CD23− B-cell lymphoma/leukemia are reviewed and described in regard to morphology, bone marrow morphological findings, Cyclin D1 immunostaining, and bcl-1 analysis. Clinical data were not available owing to the varied clinical sources of the specimens. Setting.—Tertiary-care academic institution. Results.—Lymph node involvement in blastic CD5+, CD23− B-cell lymphoma was diffuse (100%) with a nodular component (33%) or focal mantle zone pattern (10%). Bone marrow involvement in blastic CD5+, CD23− B-cell lymphoma was seen in only 27% of cases and was composed predominantly of small, slightly irregular lymphocytes. Cyclin D1 was demonstrated in 60% of the 15 cases analyzed and more sensitive in B5–fixed tissue. Bcl-1 (performed in 5 cases) was not detected in the 4 cases of blastic CD5+, CD23− B-cell lymphoma analyzed and was detected in the case of the prolymphocytoid MCL. Cyclin D1 was demonstrated in all 4 bcl-1 negative cases and was negative in the bcl-1 positive prolymphocytoid MCL. Conclusion.—Careful analysis of clinical data, morphology, immunophenotype, Cyclin D1 expression, and molecular analysis are required to differentiate the unusual large cell variants of MCL from other processes.

Follicular large-cell lymphoma treated with intensive chemotherapy: an analysis of 89 cases included in the LNH87 trial and comparison with the outcome of diffuse large B-cell lymphoma. Groupe d'Etude des Lymphomes de l'Adulte.

1997 ◽  
Vol 15 (4) ◽  
pp. 1654-1663 ◽  
Author(s):  
D Wendum ◽  
C Sebban ◽  
P Gaulard ◽  
B Coiffier ◽  
H Tilly ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Prognostic Factors ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Intensive Chemotherapy ◽  
Large B Cell Lymphoma ◽  
Beta 2 Microglobulin

PURPOSE The aims of this study were as follows: (1) to analyze clinical, histopathologic characteristics, treatment outcome, and prognostic factors of patients with follicular large-cell lymphoma (FLCL); and (2) to compare them with those of patients with diffuse large B-cell lymphoma (DLCL) treated in the same therapeutic trial. PATIENTS AND METHODS Eighty-nine FLCL patients who were histologically reviewed and who received an intensive chemotherapy regimen according to the LNH 87 protocol were analyzed and compared with 1,096 B-cell DLCL patients included in the same protocol. RESULTS After intensive induction treatment, 59 patients (67%) achieved a complete remission [CR]. Estimated 5-year survival was 59%, and estimated 5-year freedom from progression (FFP) was 39%. Prognostic factors associated with shorter FFP were age greater than 60 years (P = .02), advanced clinical stage (P = .01), abnormal lactic dehydrogenase (LDH) level (P = .02), abnormal beta-2 microglobulin (P = .02), B symptoms (P = .03), bone marrow involvement (P = .04), and high expression of bcl-2 protein (P = .05). When compared with B-cell DLCL patients, FLCL patients were younger (P = .02), had a better Eastern Cooperative Oncology Group (ECOG) status (P = .05), less bulky mass (P = .04), more advanced clinical stages (P < .001), and more bone marrow involvement (P = .02). No significant difference was observed between FLCL and DLCL patients for response to therapy (67% v 67% of CR), 5-year overall survival (58% v 51%), 5-year disease-free survival (53% v 57%), or FFP survival (39% v 43%). CONCLUSION FLCL patients have a favorable response rate and survival when treated with intensive chemotherapy. Their outcome is similar to that of B-cell DLCL patients, and a long-term FFP is observed for a substantial number of patients. Some adverse prognostic factors (including those of the International Prognostic Index, bone marrow involvement, and beta-2 microglobulin) have been identified to define a subset of patients who require other therapeutic approach.

SOX11 is useful in differentiating cyclin D1-positive diffuse large B-cell lymphoma from mantle cell lymphoma

2012 ◽  
Vol 61 (4) ◽  
pp. 685-693 ◽  
Author(s):  
Shih-Chuan Hsiao ◽  
Inmaculada Ribera Cortada ◽  
Luis Colomo ◽  
Hongtao Ye ◽  
Hongxiang Liu ◽  
...  
Keyword(s):  
B Cell ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Large B Cell

Expression of X-Linked Inhibitor of Apoptosis Protein in Reactive Lymphoid Tissues, Non-Hodgkin’s Lymphomas, and Hodgkin’s Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4655-4655
Author(s):  
James A. Strauchen ◽  
David Burstein
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Hodgkin Disease ◽  
Large B Cell Lymphoma ◽  
Apoptosis Protein ◽  
Mantle Cell ◽  
Large B Cell

Abstract X-linked inhibitor of apoptosis protein (XIAP) is an important regulator of apoptosis which binds to and inhibits caspases-3, -7 and -9, blocking the caspase 9-mediated apoptosis pathway. This pathway is activated by p53 and DNA damage and may be an important determinant of responsiveness to chemotherapy. Apoptosis also plays a major role in the regulation of follicle center B-cell proliferation and BCL2-mediated inhibition of apoptosis is a key factor in B-cell lymphomagenesis. In this study we examined the expression of XIAP in 65 reactive and neoplastic lymphoid proliferations utilizing a monoclonal antibody to XIAP (#610763 BD Biosciences, San Jose, CA) and immunohistochemistry with avidin-biotin-complex immunoperoxidase technique on formalin-fixed, paraffin-embedded sections. In reactive lymph nodes and tonsils, expression of XIAP was limited to large noncleaved cells in follicle centers (5 of 6 cases). XIAP was absent in plasmacytoma (3 cases) and small lymphocytic lymphoma/chronic lymphocytic leukemia (1 case). XIAP was expressed in follicular lymphoma, predominantly in large noncleaved cells (6 of 9 cases) and in diffuse large B cell lymphoma (11 of 16 cases), including cases of T-cell/histiocyte-rich diffuse large B cell lymphoma (2 cases), primary mediastinal large B cell lymphoma (1 case), and posttransplantation diffuse large B cell lymphoma (1 case). XIAP was consistently expressed in Burkitt and Burkitt-like lymphoma (3 of 3 cases) and anaplastic large cell lymphoma (3 of 3 cases) and in one case of adult T cell leukemia/lymphoma. XIAP was variably expressed in marginal-zone B cell lymphoma, predominantly in large blasts (2 of 4 cases) and in mantle cell lymphoma (2 of 3 cases). XIAP was not detected in peripheral T cell lymphoma, unspecified (1 case), extranodal NK/T cell lymphoma, nasal type (1 case), precursor B cell lymphoblastic leukemia (1 case), or granulocytic sarcoma (1 case). XIAP was consistently expressed in the Reed-Sternberg and mononuclear Reed-Sternberg-variant cells of classical Hodgkin disease (9 of 9 cases) and the L+H Reed-Sternberg-variant cells of nodular lymphocyte predominance Hodgkin disease (3 of 3 cases). XIAP is expressed across a broad range of lymphoproliferative disorders, including classical and nodular lymphocyte predominance Hodgkin disease, diffuse large B cell lymphoma, follicular lymphoma, Burkitt lymphoma, marginal-zone and mantle cell lymphoma, and anaplastic large cell lymphoma. XIAP appears to be selectively expressed in the proliferating elements of these lymphomas. The possible prognostic and therapeutic significance of XIAP expression needs to be determined.

Rituximab Maintenenance Therapy in CD20+ B-Cell Non-Hodgkin-Lymphoma – Final Results of a Multicenter Prospective Randomised Phase II Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1707-1707
Author(s):  
Mathias Witzens-Harig ◽  
Axel Benner ◽  
Michael Rieger ◽  
Fabienne McClanahan ◽  
Manfred Hensel ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Observation Group ◽  
Who Grade ◽  
Rituximab Maintenance ◽  
Mantle Cell

Abstract Abstract 1707 Poster Board I-733 Background Clinical and pharmacokinetic data suggest that the effect of rituximab could be improved by prolonged exposure to the drug. To test for this hypothesis we performed a prospective randomized trial of rituximab maintenance therapy in patients (pts) with CD20+ B-cell Non-Hodgkin-Lymphoma. Methods After completion of standard treatment pts with CD20+ B-cell lymphoma were randomized to either observation or maintenance therapy with rituximab (375 mg/m2) administered every 3 months for 2 years. Both pts after first line therapy and pts after relapse treatment were included in the study. Pts with aggressive lymphoma were enrolled if they had achieved a complete response (CR) after initial treatment. Pts with aggressive lymphoma with residual tumor mass underwent positron emission tomography (PET) and qualified for randomization if this examination showed no signs of tumor activity. Pts with indolent lymphoma were eligible for the study if at least a partial response (PR) was achieved. Primary endpoint of the study was event free survival (EFS), secondary endpoints were relapse rate (RR), relapse free survival (RFS) and overall survival (OS). EFS and OS were analysed using an asymptotic logrank test, RFS using a competing risk model and RR using Fisher's exact test. Results After recruitment of 171 pts the planned final analysis was performed on an intention to treat basis. Complete data sets of 163 pts were evaluable. 91 (62%) pts were male, median age was 58 years, 130 pts (80%) hat one previous therapy, 27 pts (17%) 2 previous therapies, 4 pts (2%) 3 previous therapies and 1 pt (1%) 4 previous therapies. At study entry, 120 pts (74%) were in CR, 2 pts (2%) in unconfirmed CR and 41 pts (25%) in PR. Histological subtypes included diffuse large cell lymphoma (67 pts), follicular lymphoma (35 pts), mantle cell lymphoma (18 pts), primary mediastinal lymphoma (16 pts), marginal zone lymphoma (7 pts), Burkitt's lymphoma (5 pts), and other lymphomas (15 pts). Age, sex, number of previous therapies, remission state and diagnoses were well balanced between the rituximab maintenance and the observation group (p>0.05). After a median follow up of 28 months, EFS (HR 0.50, 95% CI 0.23-1.09, p=0.037,) and RFS (HR 2.52, 95% CI 1.11-5.70 p=0.03) were superior for the maintenance group. In regards to diagnostic subgroups, EFS was in particular prolonged in pts with mantle cell lymphoma (p=0.055, one sided logrank test) and to a lesser extent in pts with follicular lymphoma (p=0.16) and diffuse large cell B cell lymphoma (p=0.18). Relapse occurred more often in the observation group than in the treatment group, however this effect was not significant (relapse rate observation group/treatment group = 2.31, 95% CI 0.86-6.75, p=0.08). There was no difference in OS between the two groups (p=0.74). Maintenance therapy was generally well tolerated: in 5 pts a WHO Grade 3 toxicity event occurred, which were arrhythmia, neuropathy, leucopenia (n=1 each) and infections (n=2). In one pt two WHO Grade 3 toxicities were observed (pain and infection). Conclusion Rituximab maintenance therapy is feasible, safe and well tolerated and improves EFS in patients with CD20+ B-cell lymphoma. In this analysis, the benefit of rituximab maintenance was particularly striking in patients with mantle cell lymphoma. This study has been continued with an amendment including additional pts with mantle cell and diffuse large cell lymphoma. Disclosures No relevant conflicts of interest to declare.

scholarly journals Bone marrow origin of a B-cell lymphoma

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 94-101
Author(s):  
LF Bertoli ◽  
H Kubagawa ◽  
GV Borzillo ◽  
PD Burrows ◽  
MT Schreeder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
Variable Region ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Low Grade ◽  
Immunoglobulin Gene ◽  
B Lineage

To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma, we produced a monoclonal antibody to a variable region idiotope on the lymphoma IgM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pre- B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma IgM kappa recognized 10% of B cells in bone marrow and blood and greater than 95% of B cells in lymphomatous lymph nodes, including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly revealed expansion of multiple clones of early B lineage cells in bone marrow, including members of the neoplastic clone. The data suggest that this lymphoma arose through a progression of transformational events beginning in bone marrow: first, creation of an oligoclonal pre- neoplastic pool of pre-B cells, subsequent conversion of a single subclone into low grade neoplastic B cells that homed to the lymph node follicles, and later progression to a more invasive form of the B-cell lymphoma.

scholarly journals CD5-Negative, CD10-Negative Low-Grade B-Cell Lymphoproliferative Disorders of the Spleen

2021 ◽  
Vol 28 (6) ◽  
pp. 5124-5147
Author(s):  
John J. Schmieg ◽  
Jeannie M. Muir ◽  
Nadine S. Aguilera ◽  
Aaron Auerbach
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Hairy Cell Leukemia ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoproliferative Disorders ◽  
Low Grade ◽  
Hairy Cell ◽  
Cell Leukemia ◽  
Red Pulp

CD5-negative, CD10-negative low-grade B-cell lymphoproliferative disorders (CD5-CD10-LPD) of the spleen comprise a fascinating group of indolent, neoplastic, mature B-cell proliferations that are essential to accurately identify but can be difficult to diagnose. They comprise the majority of B-cell LPDs primary to the spleen, commonly presenting with splenomegaly and co-involvement of peripheral blood and bone marrow, but with little to no involvement of lymph nodes. Splenic marginal zone lymphoma is one of the prototypical, best studied, and most frequently encountered CD5-CD10-LPD of the spleen and typically involves white pulp. In contrast, hairy cell leukemia, another well-studied CD5-CD10-LPD of the spleen, involves red pulp, as do the two less common entities comprising so-called splenic B-cell lymphoma/leukemia unclassifiable: splenic diffuse red pulp small B-cell lymphoma and hairy cell leukemia variant. Although not always encountered in the spleen, lymphoplasmacytic lymphoma, a B-cell lymphoproliferative disorder consisting of a dual population of both clonal B-cells and plasma cells and the frequent presence of the MYD88 L265P mutation, is another CD5-CD10-LPD that can be seen in the spleen. Distinction of these different entities is possible through careful evaluation of morphologic, immunophenotypic, cytogenetic, and molecular features, as well as peripheral blood and bone marrow specimens. A firm understanding of this group of low-grade B-cell lymphoproliferative disorders is necessary for accurate diagnosis leading to optimal patient management.

scholarly journals Expression of the retinoblastoma protein in low-grade B-cell lymphoma: relationship to cyclin D1

Blood ◽  
1996 ◽  
Vol 88 (1) ◽  
pp. 268-276 ◽  
Author(s):  
LR Zukerberg ◽  
WF Benedict ◽  
A Arnold ◽  
N Dyson ◽  
E Harlow ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
B Cell ◽  
Cyclin D1 ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Adenovirus E1a ◽  
Mantle Cell

Abstract The product of the retinoblastoma tumor-suppressor gene (pRB), a nuclear phosphoprotein that regulates transcription factors such as E2F, is involved in cell cycle control and differentiation. Its activity is regulated by phosphorylation; the underphosphorylated form inhibits transcription whereas the highly phosphorylated form is inactive. Cyclin D1 and its associated kinase (CDK 4/6) phosphorylate pRB in vitro, and therefore are thought to contribute to the regulation of pRB function. To examine the effect of cyclin D1 overexpression on pRB in primary tumor tissue, we studied pRB expression in low-grade B- cell neoplasms, with particular regard to mantle cell lymphoma, which is characterized by cyclin D1 (bcl-1) overexpression. pRB expression was studied by immunostaining with a well-characterized anti-pRB antibody; the phosphorylation status of pRB was examined by immunoblots; and the functional binding capacity of pRB was examined by in vitro binding to adenovirus E1A protein. We studied 3 reactive lymph nodes, 28 low grade B-cell lymphomas, 4 cases of hairy cell leukemia (HCL) and 3 plasmacytomas. Reactive lymph nodes showed intense pRB staining of germinal centers, with strongest (2+) staining in the large cells (centroblasts) of the proliferating (dark) zone and weak or no staining of small lymphocytes, including those of the mantle zone. In B- chronic lymphocytic leukemia (B-CLL) (4 cases), follicular lymphoma (3 cases) and mucosa-associated (MALT) lymphoma (3 cases) strong (2+) pRB staining was limited to centroblasts in reactive and neoplastic follicles and occasional proliferation centers, with only faint staining of small lymphoid cells. In contrast, 15 of 16 cases of mantle cell lymphoma showed strong (1–2+) staining of most cells; one blastoid mantle cell lymphoma showed only faint pRB staining. All cases of (HCL) and plasmacytoma showed strong pRB staining. Although most lymphomas with strong pRB expression were cyclin D1(+), three cyclin D1(+) cases showed only weak pRB expression (1 B-CLL, 1 blastoid mantle cell, 1 unclassifiable low grade B-cell lymphoma). Conversely, of the 4 pRB(+) HCLs and 3 pRB(+) plasmacytomas, only 1 of each was cyclin D1(+). pRB appeared to exist primarily in the underphosphorylated (fastest migrating) form on Western blot, despite the fact that cyclin D1 was complexed to CDK4, a form in which it normally phosphorylates pRB. In addition, pRB appeared to be unmutated, because it bound normally to the adenovirus E1A protein and showed nuclear localization by immunostaining. We conclude that most cases of mantle cell lymphoma, HCL, and plasmacytoma show high levels of pRB in contrast to follicle center lymphoma and small lymphocytic lymphoma; however, pRB expression does not appear to be consistently related to cyclin D1 overexpression. The pRB appears to be unmutated and underphosphorylated, and therefore should be in its active form. Our data from primary lymphoma tissue suggests that overexpression of cyclin D1, whereas tumorigenic, does not lead to pRB loss or hyperphosporylation. Thus, the mechanism by which cyclin D1 contributes to tumorigenesis and the significance of the restricted expression of pRB in low-grade lymphoid neoplasms remain to be determined.

B-Cell Depletion for Two Years after Autologous Stem Cell Transplant Reduces Lymphoma Relapse but Induces Prolonged Hypogammaglobulinemia beyond the Rituxan Maintenance Period.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4480-4480
Author(s):  
Seah H. Lim ◽  
William V. Esler ◽  
Yana Zhang ◽  
Jian Zhang ◽  
Phillip O. Periman ◽  
...  
Keyword(s):  
High Risk ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Maintenance Period ◽  
Mantle Cell

Abstract Although autologous stem cell transplant (ASCT) may benefit patients with relapsed or high risk non-Hodgkin’s lymphoma (NHL), many patients still relapse and die of their disease. Most relapses occur during the first three years after transplant. In an attempt to reduce disease relapses, we have applied a maintenance regimen to patients after ASCT for B-cell NHL. In this regimen, all patients received low dose rituximab infusion (375 mg/m2 for one day only) every three months starting D+100 for a total of 2 years or until disease relapse. We reasoned that rituxan infusion given for only one day every three months may be sufficient to prevent disease relapse during this post-transplant period when any residual tumor bulk is likely low. Fifteen patients (eight men, seven women) with high-risk B-cell lymphoma have been treated. Their diagnoses: advanced mantle cell lymphoma in first complete remission (CR1) (8), refractory advanced marginal zone lymphoma (2), refractory follicular large cell lymphoma (1), high risk T-cell rich B-cell NHL in CR1 (1), Stage IV diffuse large cell lymphoma in CR1 (1) and relapsed B-cell NHL in CR2 (2). The median age was 59 years (range 38–72 years). CR was achieved using R-CHOP (10) or R-DHAP/R-ICE (5) and autologous hematopoietic stem cells were harvested during hematopoietic recovery from the last course of chemo-immunotherapy. With a median follow-up of 46 months (range 12–66) for the group and 47 months (range 16–66) for patients with advanced mantle cell lymphoma, the projected 5.5 years relapse-free survival for the group is 100% and the overall survival 80%. Two patients with mantle cell lymphoma died, one due to metastatic breast cancer and another a stroke at 40 and 41 months respectively. Unlike patients who underwent ASCT without rituximab, in whom B-cell recovery occurred between 3–6 months, we observed severe delays in the immunoglobulin recoveries in these patients (Figure 1). With a median immunoglobulin follow-up of 28 months (range 6–64), none of the fifteen patients showed normalization of total IgG. Two patients achieved a normalized total IgA and two a normalized total IgM. This hypogammaglobulinemia persists beyond the rituxan maintenance period. The median time to attainment of 75% normal level of immunoglobulin is 36 months for IgG, 48 months for IgA and not reached for IgM. The severe immunoglobulin deficiencies may be clinically relevant. Six of fifteen patients developed recurrent upper respiratory tract infection. No fatal infection was observed among any of the patients. Our results, therefore, suggest that low dose rituximab administration every three months after ASCT for high-risk B-cell lymphoma may prevent lymphoma relapse. However, this is associated with severe and prolonged delays in immunoglobulin recovery beyond the rituxan maintenance period. Careful monitoring of the immunoglobulin recovery and intervention as appropriate should be done routinely in these patients. Figure Figure

scholarly journals Bone marrow origin of a B-cell lymphoma

Blood ◽  
1988 ◽  
Vol 72 (1) ◽  
pp. 94-101 ◽  
Author(s):  
LF Bertoli ◽  
H Kubagawa ◽  
GV Borzillo ◽  
PD Burrows ◽  
MT Schreeder ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Cell Lymphoma ◽  
Variable Region ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
Low Grade ◽  
Immunoglobulin Gene ◽  
B Lineage

Abstract To search for precursors of the neoplastic B cells in a patient with a nodular lymphoma, we produced a monoclonal antibody to a variable region idiotope on the lymphoma IgM heavy chain. Clonal ancestors of the lymphoma cells were identified by this marker among bone marrow pre- B cells (5% to 26%). A second antiidiotype (anti-Id) antibody specific for the complete lymphoma IgM kappa recognized 10% of B cells in bone marrow and blood and greater than 95% of B cells in lymphomatous lymph nodes, including one obtained after tumor conversion to a diffuse large cell lymphoma. Immunoglobulin gene analysis surprisingly revealed expansion of multiple clones of early B lineage cells in bone marrow, including members of the neoplastic clone. The data suggest that this lymphoma arose through a progression of transformational events beginning in bone marrow: first, creation of an oligoclonal pre- neoplastic pool of pre-B cells, subsequent conversion of a single subclone into low grade neoplastic B cells that homed to the lymph node follicles, and later progression to a more invasive form of the B-cell lymphoma.

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