Pattern of Mir-155 and PU.1 Expression in CLL/SLL and Aggressive Lymphomas

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4600-4600
Author(s):  
Tomas Stopka ◽  
Karin Vargova ◽  
Hana Huskova ◽  
Pavel Burda ◽  
Nikola Curik ◽  
...  
Keyword(s):  
B Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Peripheral T Cell Lymphoma ◽  
Lymphoid Malignancies ◽  
Mantle Cell ◽  
Prognostic Groups ◽  
Nfkb Pathway

Abstract Abstract 4600 MicroRNA miR-155 represents a candidate pathogenic factor in chronic lymphocytic leukemia (CLL) and lymphomas (Eis PS, et al. 2005, Fulci V, et al. 2007, Calin GA, et al. 2005, Kluiver J, et al. 2005, Metzler M, et al. 2004, van den Berg A, et al. 2003., Vargova K. et al 2011). In diffuse large B-cell lymphoma (DLBCL) expression of miR-155 was associated with NFkB pathway (Rai et al., 2008). In addition, increased miR-155 levels were associated with more aggressive (Activated B-cell like) DLBCL (Eis et al. 2005). The targets of up-regulated miR-155 apparently include a key hematopoietic transcription factor PU.1. Down-regulation of PU.1 represents an important and critical step for both myeloid as well as lymphoid tumorigenesis. We herein found the increased levels of miR-155 coupled with downregulation of its target PU.1 are frequent events in B cells of a vast majority of CLL patients (N=169). To advance understanding of miR-155 and PU.1 in lymphoid malignancies we studied lymph node biopsies derived from patients with lymphomas. We show that increased miR-155 levels are also found in DLBCL (N=31, P < 0.0001), Hodgkin lymphoma (HL, N=22, P < 0.0001), follicular lymphoma (FL, N=23, P < 0.001), small lymphocytic lymphoma (SLL, N=12, P < 0.01), and marginal zone lymphoma (MZL, N=11, P < 0.01). The miR-155-overexpressing tumors display downregulation of PU.1. In contrast, peripheral T cell lymphoma (T-NHL, N=6) and mantle cell lymphoma (MCL, N=7) expressed miR-155 and PU.1 comparably as control lymph nodes. Our data indicate that expression pattern of miR-155 and its target PU.1 represents a hallmark of some but not all lymphoid malignancies. Interestingly, the miR-155/PU1 levels vary substantially within each diagnosis, therefore, our aim is to further analyze the occurrence of this relationship in different prognostic groups and analyze the clinical outcome as well. (Grants: NT10310-3/2009 & NT11218-6/2010, MPO FR-TI2/509, GAUK251135 82210 & 251070 45410, SVV-2011-262507) Disclosures: No relevant conflicts of interest to declare.

scholarly journals The biology behind B-cell lymphoma 2 as a target in chronic lymphocytic leukemia

2016 ◽  
Vol 7 (6) ◽  
pp. 321-329 ◽  
Author(s):  
Valentín Ortíz-Maldonado ◽  
Pablo Mozas ◽  
Julio Delgado
Keyword(s):  
Clinical Trials ◽  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Mitochondrial Pathway ◽  
Therapeutic Agents ◽  
Lymphocytic Leukemia ◽  
Hallmarks Of Cancer ◽  
Lymphoid Malignancies

B-cell lymphoma 2 (BCL2)-type proteins are key regulators of the intrinsic or mitochondrial pathway for apoptosis. Since escape from apoptosis is one the main ‘hallmarks of cancer’, BCL2 inhibitors have emerged as promising therapeutic agents for diverse lymphoid malignancies, particularly chronic lymphocytic leukemia (CLL). Multiple clinical trials have shown efficacy of these agents in patients with relapsed/refractory disease with a favorable toxicity profile. Moreover, some clinical trials indicate that combination with monoclonal antibodies and other novel agents may enhance their effect.

Umbilical Cord Blood (UCB) Transplantation after Non-Myeloablative (NMA) Conditioning for Advanced Follicular Lymphoma, Mantle Cell Lymphoma and Chronic Lymphocytic Leukemia: Low Transplant-Related Mortality and High Progression-Free Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2900-2900 ◽  
Author(s):  
Juliet N. Barker ◽  
Daniel J. Weisdorf ◽  
Todd E. DeFor ◽  
Claudio G. Brunstein ◽  
John E. Wagner
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cumulative Incidence ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Lymphoid Malignancies ◽  
Mantle Cell ◽  
Related Mortality

Abstract A graft-versus-leukemia/lymphoma (GVL) effect after allografting has been documented for advanced or refractory indolent B cell Non-Hodgkin’s lymphoma (NHL), mantle cell lymphoma (MCL), and chronic lymphocytic leukemia (CLL). However, widespread application of allografting in these patients has been limited by lack of suitable donors as well as high transplant-related mortality (TRM) when conventional myeloablative conditioning is used. NMA conditioning is associated with reduced TRM and has been successful in patients with these B cell lymphoid malignancies transplanted with HLA-matched sibling donors. Therefore, to extend access to transplant, we evaluated the effectiveness of NMA conditioning followed by unrelated donor UCB transplantation (UCBT) in patients with these diseases. Patients received 50 mg/kg cyclophosphamide, 200 mg/m2 fludarabine and 200 cGy TBI with cyclosporine and mycophenolate mofetil immunosuppression. Sixteen patients with advanced or refractory follicular NHL (n=7), MCL (n=3), or CLL (n=6) were transplanted between 10/3/2001 and 11/30/2004. Median patient age was 51 years (range, 37–67) and weight was 81 kg (range, 60–102). Patients received single (n=4) or double unit (n=12) 4–6/6 HLA-matched (intermediate resolution DNA typing at HLA-A and B; high resolution HLA-DRB1) UCB grafts with a median infused cell dose of 3.5 x 107 NC/kg (range, 2.6–4.6) and 5.0 x 107 CD34+ cells/kg (range, 2.6–14.3). Cumulative incidence of sustained donor engraftment was 81% (95%CI: 62–100) with a median day of neutrophil recovery of 8 days (range, 5–30). Two of the 3 patients with failure of donor engraftment had received only a single cycle of CVP chemotherapy immediately prior to UCBT. Twelve patients had grade 2–4 acute graft-versus-host disease (GVHD) (9 grade 2, 2 grade 3, and 1 grade 4) for a cumulative incidence of 75% (95%CI: 49–100) by day 100, while 6 patients had extensive chronic GVHD for a cumulative incidence of 39% (95%CI: 14–64) by 1 year. The cumulative incidence of TRM at 6 months was 6% (95%CI: 0–17). At a median follow-up of 22 months (range 7–42), 4 patients (3 follicular NHL, 1 CLL) have died (3 with progressive disease and 1 with infection) whereas 12 are alive in complete remission with a probability of progression-free survival of 63% (95%CI: 49–87) at 1 year. Two follicular NHL patients, both refractory to rituximab pre-transplant, required the addition of rituximab post-transplant to achieve sustained remission. Also, 2 of 3 patients (both with CLL) who had transient donor engraftment but subsequent autologous recovery are in remission at 14 and 15 months after UCBT, respectively. In conclusion, these preliminary results suggest that UCBT after NMA conditioning is an effective treatment for B cell lymphoid malignancies in adults with a low rate of TRM. Based on these data, and data in other patients undergoing NMA transplantation, therapy immediately prior to UCBT is likely an important factor in donor engraftment. A GVL effect is suggested and may be augmented by the addition of rituximab. This strategy extends treatment options for patients with advanced or refractory follicular NHL, mantle cell NHL, and CLL who are otherwise fit and warrants further investigation. Finally, given the low TRM, patient referral prior to the development of refractory disease should be strongly considered and may further improve outcomes.

Safety and Efficacy of Bendamustine with or without Rituximab in the Treatment of Heavily Pretreated Patients with Haematological Malignancies: A Multicenter Retrospective Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4945-4945 ◽  
Author(s):  
Luigi Rigacci ◽  
Benedetta Puccini ◽  
Alberto Bosi ◽  
Sergio Cortelazzo ◽  
Sergio Storti ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Heavily Pretreated ◽  
Pretreated Patients ◽  
Large B Cell

Abstract Bendamustine is an purine analog alkylating agent with marked efficacy in haematological malignancies either when given as monotherapy or in combination with rituximab. The efficacy and safety of this drug was investigated in heavily pretreated patients (pts) with hematological malignancies. A total of 44 patients (median age 63 years ranging from 22–87) from 6 Italian centers treated with bendamustine alone or in combination with rituximab were analyzed in this retrospective study. The diagnoses were multiple myeloma (n=2), chronic lymphocytic leukemia or small lymphocytic lymphoma (n=19), diffuse large B cell lymphoma (n=7), follicular lymphoma (n=8), mantle cell lymphoma (n=4), marginal zone lymphoma (n=2), Hodgkin’s disease (n=1) and peripheral T cell lymphoma (n=1). All pts received bendamustine 60–90 mg/m2 at day 1+2, alone or in combination with rituximab 375 mg/m2 (n=35) at day 1 of each cycle given every 21 or 28 days. The pts were heavily pretreated with a median of 3 previous treatments (range 1–8); 37 pts had previously received rituximab and 9 pts had undergone autologous transplantation. Prior to receiving bendamustine, 14 pts had relapsed disease, 7 had refractory disease and 23 were progressing during therapy. The median number of bendamustine cycles was 3 (range 1–8); 11 pts were still on treatment at the time of this analysis. Patients who completed therapy with at least 1 cycle of chemotherapy were evaluated for response and toxicity; pts in continuous therapy were evaluated for toxicity only. Of 33 pts evaluable for response 7 pts achieved a CR (21%) and 14 a PR (42%) resulting in an ORR of 64%. The remaining 12 pts were non-responders. No differences in the results were observed between groups with different bendamustine doses or scheduling. The best results were obtained in 10 evaluable pts with indolent lymphoma (4 CR, 6 PR) and in 9 pts with chronic lymphocytic leukemia (1 CR, 6 PR). Two evaluable pts with mantle cell lymphoma obtained a response (1 CR, 1 PR). By contrast, only 1 pt with diffuse large B cell lymphoma of 6 patients evaluable for response obtained a CR: the other 5 were non-responders. No pt with myeloma, Hodgkin’s disease or T cell lymphoma achieved a response. After a median follow-up of 4 months, 80% of pts were alive. During 150 treatment cycles, 2 pts experienced grade 4 thrombocytopenia and 1 experienced grade 4 neutropenia; non-hematological toxicity was mild. In conclusion, this retrospective analysis shows that treatment with bendamustine, alone or in combination with rituximab, is a safe and effective regimen in heavily pretreated pts. The best results were obtained in indolent lymphoma: the data in mantle cell lymphoma were also encouraging. No lack of efficacy can be inferred in pts with diffuse large B cell lymphoma, due to the refractory nature of their disease and the advanced age of this particular group (median age 76 years ranging from 67–87).

scholarly journals Apoptotic Blocks in Primary Non-Hodgkin B Cell Lymphomas Identified by BH3 Profiling

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1002
Author(s):  
Ryan N. Rys ◽  
Claudia M. Wever ◽  
Dominique Geoffrion ◽  
Christophe Goncalves ◽  
Artin Ghassemian ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Poor Response ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
High Grade ◽  
Microtubule Inhibitors ◽  
Mantle Cell ◽  
Induced Apoptosis

To determine causes of apoptotic resistance, we analyzed 124 primary B cell NHL samples using BH3 profiling, a technique that measures the mitochondrial permeabilization upon exposure to synthetic BH3 peptides. Our cohort included samples from chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL), high-grade B cell lymphoma with translocations in MYC and BCL2 (HGBL-DH), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). While a large number of our samples displayed appropriate responses to apoptosis-inducing peptides, pro-apoptotic functional defects, implicating BAX, BAK, BIM or BID, were seen in 32.4% of high-grade NHLs (12/37) and in 3.4% of low-grade NHLs (3/87, p < 0.0001). The inhibition of single anti-apoptotic proteins induced apoptosis in only a few samples, however, the dual inhibition of BCL2 and MCL1 was effective in 83% of samples, indicating MCL1 was the most common cause of lack of response to the BCL2 inhibitor, venetoclax. We then profiled Toledo and OCI-Ly8 high-grade lymphoma cell lines to determine which drugs could reduce MCL1 expression and potentiate venetoclax responses. Doxorubicin and vincristine decreased levels of MCL1 and increased venetoclax-induced apoptosis (all p < 0.05). Overall, in primary NHLs expressing BCL2 that have no defects in pro-apoptotic signaling, a poor response to venetoclax is primarily due to the presence of MCL1, which may be overcome by combining venetoclax with doxorubicin and vincristine-based chemotherapy or with other anti-microtubule inhibitors.

scholarly journals Flow Cytometry in the Diagnosis of Canine B-Cell Lymphoma

2021 ◽  
Vol 8 ◽  
Author(s):  
Fulvio Riondato ◽  
Stefano Comazzi
Keyword(s):  
Flow Cytometry ◽  
B Cell ◽  
Prognostic Markers ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphoid Malignancies ◽  
Large B Cell Lymphoma ◽  
Mantle Cell ◽  
Lymphoma Subtype

B cell lymphoma (BCL) is a heterogeneous group of lymphoid malignancies which comprise the majority of canine lymphomas. Diffuse large B cell lymphoma is the most common lymphoma subtype in dogs but other subtypes (e.g., marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, and others) have been described. This review aims to explore the use of flow cytometry to refine the diagnosis of canine BCL. Particular emphasis will be given to the possible identification of peculiar immunotypes, putative prognostic markers, staging and minimal residual disease.

Analysis of Mantle Cell Lymphoma Patients Reveals Novel Regulatory Circuits Involving MicroRNAs and Their Targets

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4624-4624
Author(s):  
Vojtech Kulvait ◽  
Vit Pospisil ◽  
Karin Vargova ◽  
Marek Trneny ◽  
Pavel Klener ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Target Gene ◽  
Zinc Finger Protein ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Differentially Expressed ◽  
Regulatory Pathways ◽  
Mantle Cell

Abstract Abstract 4624 Mantle cell lymphoma (MCL) represents B-cell lymphoma derived from the mantle zone that surrounds normal germinal center follicles. Pathophysiology of this hardly curable disease involves t(11,14)(q13,q32) translocation which leads to upregulation of Cyclin D1(CCND1). Recently, microRNAs were demonstrated to significantly modify MCL pathogenesis (Jian-Jun Zhao et al. 2010) and therapy responsiveness (Jiang et al. 2010). In order to broaden our knowledge of regulatory pathways in MCL we searched for differentially expressed microRNAs and their differentially expressed mRNA targets between MCL samples and control samples. Samples consist of magnetically separated B cells derived from peripheral blood. We used 1) Microarray mRNA hybridization [Affymetrix Human Genome U133 Plus 2.0 Array, N(MCL)=5, N(control)=5] and 2) microRNA profiling [TaqMan® Array Human MicroRNA Card A v2.0 technology, N(MCL)=5, N(control)=5] followed by statistical analysis [limma (Smyth 2005)]. Differentially regulated targets of the deregulated microRNAs were selected from the databases involving both predicted (Betel et al. 2007) or confirmed (Hsu et al. 2010) target mRNAs. Among the most significant upregulated microRNAs (exceeding 10 fold) are miR-9, miR-124 and miR-183. We have found that upregulated miR-9 has confirmed downregulated target gene PRDM1 (PR domain zinc finger protein 1) which plays a role in B cell maturation (Turner et al. 1994) and may act as a tumor suppressor (Pasqualucci et al. 2006). Upregulation of miR-9 and downregulation of its targets was recently demonstrated in Burkitt lymphoma (Onnis A et al. 2010) and Hodgkin lymphoma (Nie K et al. 2008). Two additional upregulated microRNAs, miR-124 and miR-183, yet not associated with lymphomas, have downregulated target gene Integrin beta-1 (CD29) which regulates survival (Fukumori et al. 2003). Among most significant downregulated microRNAs is miR-101 (FC=-7). Downregulated microRNA miR-101 has known oncogene N-Myc (MYCN) as upregulated confirmed target and DNA (cytosine-5)-methyltransferase 3A (DNMT3A) as upregulated target. Overexpression of a well known hematopoietic oncogene MYCN and epigenetic repressor DNMT3A may represent additional pathogenesis-related factors in MCL. Our data support importance of the candidate mechanisms involving microRNAs and their target programs in pathogenesis of MCL. They are currently extended on a larger patient cohort by analyzing expression and functional significance of the candidate microRNAs. (Grants: NT10310-3/2009, MPO FR-TI2/509, NPVII 2B06077, MSM 0021620806, LC 06044, SVV-2011-262507). Disclosures: No relevant conflicts of interest to declare.

Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) Is a New Biomarker for Mantle Cell Lymphoma: Expression, Localization, and Phosphorylation Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1767-1767
Author(s):  
Tomas Stopka ◽  
Jarmila Vargova ◽  
Karina Vargova ◽  
Nina Dusilkova ◽  
Vojtech Kulvait ◽  
...  
Keyword(s):  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Differentially Expressed Genes ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Kinase Substrate ◽  
Mantle Cell

Abstract Mantle cell lymphoma (MCL) is a relatively distinct B-cell non-Hodgkin lymphoma subtype with aggressive and often recurrent clinical course. At diagnosis, MCL often manifests with leukemization, a feature more common to chronic lymphocytic leukemia (CLL). Common features and differences between MCL and CLL were not yet explored by comprehensive global approaches, despite such understanding potentially being very neat for deciphering pathogenesis and tailoring therapies of these clinically distinct diseases. In our study, we have compared MCL(n=10), CLL(n=10) and normal control(n=8) B-cell samples using the Affymetrix Human Genome HG-U133 Plus 2.0 Array. We studied different mRNA levels of ~47.000 transcripts represented on the array. The comparative analyses identified a set of 892 differentially expressed genes between MCL and NBC; and 774 differentially expressed genes between CLL and NBC. In order to find MCL/CLL-specific biomarkers we focused on the intersection of differently expressed genes in both groups (CLL vs NBC and MCL vs NBC). There were 222 mRNAs in the intersection, 216 of them were deregulated in the same direction in both groups while 6 mRNAs were deregulated in the opposite direction. This set of 6 disease-specific mRNAs contained previously reported biomarkers (CD200, LEF1), and also the Myristoylated alanine-rich C-kinase substrate (MARCKS) that has not yet been studied in MCL. Thus we utilized the validation patient groups (NMCL=6, NCLL=8) and confirmed differential expression of MARCKS on protein levels by flow cytometry and immunofluorescence. As MARCKS was previously shown to either bound to the cell membrane, to reside in the cytosol, or alternatively become transmitted to nuclei, we investigated subcellular localization of MARCKS using immunofluorescence (IF). The cytoplasmic MARCKS signal in MCL was significantly higher than in CLL while the opposite was observed for the nuclear IF signal. The ratio between cytoplasmic and nuclear signal was 2.5 for MCL and 0.8 for CLL (p < 0,0001). The active forms of MARCKS were shown to become phosphorylated on serineresidues and this prompted us to study the phosphorylation forms of MARCKS in MCL. Indeed, one of the residues, Ser159/163, was hyperphosphorylated in the MCL cytoplasm and its level and distribution markedly differed from CLL or NBC. We next searched for regulatory mechanisms upstream of the MARCKS expression in MCL vs CLL. MARCKS is a predicted target of several microRNAs (according to DIANA-TarBase v7.0), among them also of miR-155 (that is differentially expressed between MCL and CLL). To further investigate the regulatory relationship between mir-155 and MARCKS we utilized a CLL cell line MEC-1 and using the CRISPR/Cas9 technology we prepared individual cell clones that were mutated within the mature miR-155 sequence that recognizes MARCKS mRNA. As expected, the miR-155-MEC-1 mutants expressed markedly higher level of MARCKS compared to the control MEC-1 cells. In conclusion, our work identified a set of six differentially expressed mRNAs when comparing MCL and CLL, among them, MARCKS. We further showed that MARCKS is differentially expressed, localized, and phosphorylated between MCL and CLL, and that MARCKS is partly controlled by oncogenic microRNA miR-155. MARCKS may play an important role in MCL pathogenesis and can serve as useful MCL biomarker. Grant support: GAČR 16-05649S & P305/12/1033, AZV: 16-27790A and 16-31586A. Institutional support: CZ.1.05/1.1.00/02.0109, UNCE 204021, LH15170, PRVOUK P24, LQ1604. Disclosures No relevant conflicts of interest to declare.

Non-Hodgkin's Lymphoma Clinical Practice Guidelines

2006 ◽  
Vol 4 (3) ◽  
pp. 258 ◽  
Author(s):  
_ _
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Aggressive Lymphoma ◽  
Molecular Characteristics ◽  
Mantle Cell ◽  
Histologic Types ◽  
Hodgkin's Lymphomas ◽  
Natural Histories

Non-Hodgkin's lymphomas (NHLs) may be classified on the basis of morphology, natural history, and immunophenotypic and molecular characteristics. These guidelines were developed for more common NHL histologic types, including chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and diffuse large B-cell lymphoma, and for less common entities with unique natural histories and therapies, such as marginal zone lymphoma, mantle cell lymphoma, and highly aggressive lymphoma subtypes, including Burkitt's, and lymphoblastic lymphomas and AIDS-related B-cell lymphomas. Certain components of the diagnosis and therapy of the various NHLs are similar. In all cases, an accurate pathologic diagnosis must first be made. For the most recent version of the guidelines, please visit NCCN.org

Homeostatic chemokines drive migration of malignant B cells in patients with non-Hodgkin lymphomas

Blood ◽  
2004 ◽  
Vol 104 (2) ◽  
pp. 502-508 ◽  
Author(s):  
Livio Trentin ◽  
Anna Cabrelle ◽  
Monica Facco ◽  
Davide Carollo ◽  
Marta Miorin ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
B Lymphocytes ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Lymphocytic Leukemia ◽  
Receptor Expression ◽  
Mantle Cell ◽  
B Cell Subsets ◽  
Almost All

Abstract This study investigated the role of several chemokines and their receptors on malignant B lymphocytes recovered from 13 patients with chronic lymphocytic leukemia (CLL), 9 with hairy cell leukemia (HCL), 5 with mantle cell lymphoma (MCL), 5 with marginal zone B-cell lymphoma (MZL), 6 with small lymphocytic lymphoma (SLL), and 5 with follicular cell lymphoma (FCL). Flow cytometry analysis demonstrated that CXCR4 and CXCR5 were expressed on all malignant and normal B cells. Considering CC receptors, CCR1 was expressed in 70% of patients with CLL and 40% of those with HCL but was lacking in patients with MCL, MZL, SLL, and normal B cells. CCR2 showed a heterogeneous pattern of expression. CCR3 was found in almost all patients with CLL and in the majority of those with HCL, whereas it was usually lacking in patients with MZL and SLL and in healthy subjects. CCR5 was expressed in patients with HCL and MCL. Migration assays showed that different chemokines, mainly CXCL12 and CXCL13, are able to trigger migration of malignant B lymphocytes. Some of these chemokines induce calcium mobilization. These data indicate that different patterns of chemokine receptor expression identify different malignant B-cell subsets and that these receptors are functional and might play a role in malignant B-cell circulation. (Blood. 2004;104:502-508)

Secondary Malignancies in Mantle Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5596-5596
Author(s):  
Sandhya Talakokkla ◽  
Renuka Mahatara ◽  
Christine A Welch ◽  
Arun Nagarajan
Keyword(s):  
Pancreatic Cancer ◽  
B Cell ◽  
Mantle Cell Lymphoma ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Secondary Malignancies ◽  
Increased Risk ◽  
Mantle Cell ◽  
Second Primaries

Abstract Background: Mantle cell lymphoma is a B cell lymphoma (CD5 +) which represents 5-10 % of Non-Hodgkin's lymphoma. Most patients have advanced disease at presentation and thus carry a poor prognosis. This type of uncommon malignant lymphoma has a distinct and recurring cytogenetic abnormality involving t(11, 14) q(13, 32). Although extra nodal involvement is common, not many cases of MCL having concomitant other malignancies are reported. We hypothesized that patients with MCL have chronic immunosuppression, comparable to chronic lymphocytic leukemia patients, and therefore are at risk for developing secondary malignancies similar to CLL patients. The aim of our study is to report the retrospective analysis of patients diagnosed with MCL and the associated secondary malignancies before or after the diagnosis of MCL. Patients and methods: The records of 41 patients who presented with MCL to "The David Lee Cancer Center" at CAMC, WVU with MCL from 2000 - 2015 were retrospectively reviewed. The number of other malignancies presenting before or after the diagnosis of MCL were analyzed. Results: The population with MCL was represented by 41, all Caucasian patients, which were 75.6% male (n = 31) and had an average age of 68.6 ± 11.3 years. Mean follow up for all patients was 23.9 ± 32.43 months. A total of 14.6% (n=6), 83.3% males, experienced a second primary. Within the second primaries 50.0% were GI cancers which included pancreatic cancer and cholangiocarcinoma while 16.7% were prostate cancer, diffuse large B-cell lymphoma or adenocarcinoma of lungs. The time to second primaries varied with 50% of the cases being diagnosed simultaneously with MCL, while 33.3% were diagnosed prior to MCL at an average time of 34.5 months, and 16.7% were diagnosed post MCL diagnosis at an average time of 18 months. Conclusion: Patients with MCL are typically CD5 positive, CD10 negative, and CD23 negative which make it different from other lymphomas like small cell lymphoma, B-cell CLL that are CD 23 positive. Rare cases of MCL may be CD5 negative or CD23 Positive. We hypothesized that MCL patients have an increased risk for developing secondary cancers due to their disease biology and from underlying chronic immunosuppression. Patients with MCL have twice the risk of developing secondary malignancies and an increased frequency of certain types of cancers such as cholangiocarcinoma & pancreatic cancer. Disclosures No relevant conflicts of interest to declare.

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