Prognosis of Follicular Lymphomas

Abstract STATs are constitutively activated in several malignancies. In primary mediastinal large B-cell lymphoma and Hodgkin lymphoma (HL), inactivating mutations in SOCS1, an inhibitor of JAK/STAT signaling, contribute to deregulated STAT activity. Based on indications that the SOCS1 mutations are caused by the B cell–specific somatic hypermutation (SHM) process, we analyzed B-cell non-HL and normal B cells for mutations in SOCS1. One-fourth of diffuse large B-cell lymphoma and follicular lymphomas carried SOCS1 mutations, which were preferentially targeted to SHM hotspot motifs and frequently obviously inactivating. Rare mutations were observed in Burkitt lymphoma, plasmacytoma, and mantle cell lymphoma but not in tumors of a non–B-cell origin. Mutations in single-sorted germinal center B cells were infrequent relative to other genes mutated as byproducts of normal SHM, indicating that SOCS1 inactivation in primary mediastinal large B-cell lymphoma, HL, diffuse large B-cell lymphoma, and follicular lymphoma is frequently the result of aberrant SHM.

Download Full-text

Elevated Mcl-1 perturbs lymphopoiesis, promotes transformation of hematopoietic stem/progenitor cells, and enhances drug resistance

Blood ◽

10.1182/blood-2010-04-281071 ◽

2010 ◽

Vol 116 (17) ◽

pp. 3197-3207 ◽

Cited By ~ 80

Author(s):

Kirsteen J. Campbell ◽

Mary L. Bath ◽

Marian L. Turner ◽

Cassandra J. Vandenberg ◽

Philippe Bouillet ◽

...

Keyword(s):

Progenitor Cells ◽

Progenitor Cell ◽

Fetal Liver ◽

Cytotoxic Agents ◽

Hematopoietic Stem ◽

Stem And Progenitor Cells ◽

Fetal Liver Cells ◽

Follicular Lymphomas ◽

The Impact

Abstract Diverse human cancers with poor prognosis, including many lymphoid and myeloid malignancies, exhibit high levels of Mcl-1. To explore the impact of Mcl-1 overexpression on the hematopoietic compartment, we have generated vavP-Mcl-1 transgenic mice. Their lymphoid and myeloid cells displayed increased resistance to a variety of cytotoxic agents. Myelopoiesis was relatively normal, but lymphopoiesis was clearly perturbed, with excess mature B and T cells accumulating. Rather than the follicular lymphomas typical of vavP-BCL-2 mice, aging vavP-Mcl-1 mice were primarily susceptible to lymphomas having the phenotype of a stem/progenitor cell (11 of 30 tumors) or pre-B cell (12 of 30 tumors). Mcl-1 overexpression dramatically accelerated Myc-driven lymphomagenesis. Most vavP-Mcl-1/ Eμ-Myc mice died around birth, and transplantation of blood from bitransgenic E18 embryos into unirradiated mice resulted in stem/progenitor cell tumors. Furthermore, lethally irradiated mice transplanted with E13 fetal liver cells from Mcl-1/Myc bitransgenic mice uniformly died of stem/progenitor cell tumors. When treated in vivo with cyclophosphamide, tumors coexpressing Mcl-1 and Myc transgenes were significantly more resistant than conventional Eμ-Myc lymphomas. Collectively, these results demonstrate that Mcl-1 overexpression renders hematopoietic cells refractory to many cytotoxic insults, perturbs lymphopoiesis and promotes malignant transformation of hematopoietic stem and progenitor cells.

Download Full-text

Treatment of follicular lymphomas

DMW - Deutsche Medizinische Wochenschrift ◽

10.1055/s-2005-916357 ◽

2005 ◽

Vol 130 (38) ◽

pp. 2149-2154 ◽

Cited By ~ 1

Author(s):

M Dreyling ◽

C Buske ◽

W Hiddemann

Keyword(s):

Follicular Lymphomas

Download Full-text

Predictive Value of Prognostic Indices in Patients with Follicular Lymphomas

Medical Oncology ◽

10.1385/mo:23:4:533 ◽

2006 ◽

Vol 23 (4) ◽

pp. 533-542 ◽

Cited By ~ 3

Author(s):

M. Radojkovic ◽

S. Ristic ◽

M. Colovic ◽

B. Mihaljevic ◽

V. Cemerikic-Martinovic

Keyword(s):

Predictive Value ◽

Prognostic Indices ◽

Follicular Lymphomas

Download Full-text

Differential expression of long non-coding RNAs are related to proliferation and histological diversity in follicular lymphomas

British Journal of Haematology ◽

10.1111/bjh.15656 ◽

2018 ◽

Vol 184 (3) ◽

pp. 373-383 ◽

Cited By ~ 4

Author(s):

Alejandro Roisman ◽

Giancarlo Castellano ◽

Alba Navarro ◽

Blanca Gonzalez-Farre ◽

Patricia Pérez-Galan ◽

...

Keyword(s):

Differential Expression ◽

Non Coding Rnas ◽

Follicular Lymphomas

Download Full-text

Low frequency of BCL-2/JH translocation in peripheral blood lymphocytes of healthy Japanese individuals

Blood ◽

10.1182/blood.v98.2.486 ◽

2001 ◽

Vol 98 (2) ◽

pp. 486-488 ◽

Cited By ~ 51

Author(s):

Masaki Yasukawa ◽

Shiro Bando ◽

Gottfried Dölken ◽

Eiji Sada ◽

Yoshihiro Yakushijin ◽

...

Keyword(s):

Follicular Lymphoma ◽

Peripheral Blood ◽

Low Frequency ◽

Peripheral Blood Lymphocytes ◽

Blood Lymphocytes ◽

Japanese Adults ◽

Japanese General Population ◽

The Difference ◽

Follicular Lymphomas ◽

Immunoglobulin Heavy Chain Genes

The incidence of follicular lymphoma differs significantly between white and Japanese individuals. Translocation between theBCL-2 and immunoglobulin heavy chain genes is detected in 85% to 90% of all follicular lymphomas in whites. Recently,BCL-2/JH translocation was detected in peripheral blood lymphocytes from more than 50% of healthy white individuals. To clarify the reason for the difference in incidence of follicular lymphoma between whites and Japanese, the frequency ofBCL-2/JH translocation in peripheral blood lymphocytes of healthy Japanese individuals was compared with that of German individuals. The prevalence of BCL-2/JHtranslocation in Japanese adults appeared to be significantly lower than that in German adults. The present data suggest that the low frequency of BCL-2/JH translocation in the Japanese general population may be one of the major reasons for the difference in incidence of follicular lymphoma between whites and Japanese.

Download Full-text

Single cell origin of bigenotypic and biphenotypic B cell proliferations in human follicular lymphomas.

Journal of Experimental Medicine ◽

10.1084/jem.167.2.582 ◽

1988 ◽

Vol 167 (2) ◽

pp. 582-597 ◽

Cited By ~ 57

Author(s):

M L Cleary ◽

N Galili ◽

M Trela ◽

R Levy ◽

J Sklar

Keyword(s):

Single Cell ◽

Somatic Mutation ◽

Southern Blot Analysis ◽

Chromosomal Translocation ◽

Nucleotide Sequence Analysis ◽

Gene Rearrangements ◽

Chromosome 18 ◽

Dna Rearrangements ◽

Follicular Lymphomas ◽

Cell Proliferations

To investigate the possible relatedness of the subpopulations that make up so-called biclonal lymphomas, we examined five bigenotypic and biphenotypic follicular lymphomas using DNA probes specific for the t(14;18) chromosomal translocation, which is a characteristic feature of these neoplasms. On Southern blot analysis, both subpopulations from four of five lymphomas contained comigrating t(14;18) DNA rearrangements, confirming the single cell origins for these neoplasms. No comigrating t(14;18) DNA rearrangements were observed in the fifth lymphoma, but nucleotide sequence analysis of cloned, breakpoint DNA showed identical t(14;18) crossovers in the two subpopulations. The migration differences of both the Ig and chromosome 18 DNA rearrangements were shown to result from somatically acquired mutations of the Ig genes from the fifth lymphoma. These studies indicate that Ig gene rearrangements and idiotope expression are not consistently stable clonal markers since they are subject to variability as a result of somatic mutation. Although translocated chromosome 18 DNA rearrangements are more reliable, they may also vary among cells of some tumors since somatic mutation can affect, as well, DNA of translocated alleles in follicular lymphomas.

Download Full-text

The gene located at chromosome 18 band q21 is rearranged in uncultured diffuse lymphomas as well as follicular lymphomas

Blood ◽

10.1182/blood.v70.1.90.bloodjournal70190 ◽

1987 ◽

Vol 70 (1) ◽

pp. 90-95

Author(s):

MS Lee ◽

MB Blick ◽

S Pathak ◽

JM Trujillo ◽

JJ Butler ◽

...

Keyword(s):

Gene Rearrangement ◽

Unknown Origin ◽

Large Cell ◽

Chromosome 18 ◽

Chromosome Fragment ◽

Karyotypic Abnormality ◽

Human Lymphoma ◽

Donor Chromosome ◽

Human Genomic ◽

Follicular Lymphomas

The karyotypic abnormality t(14;18)(q32;q21) is reported to occur in 75% of follicular lymphomas. This translocation results in the rearrangement of a putative oncogene bcl-2, which resides at chromosome 18 band q21 (the 18q21 gene). Using two human genomic DNA fragments cloned from the chromosome 18 band q21 as probes, we analyzed 65 uncultured human lymphoma samples by the Southern blot technique. The 18q21 gene was rearranged in 18 of 26 (69%) follicular lymphomas, 3 of 5 (60%) follicular lymphomas transformed to large cell lymphomas, 8 of 20 (40%) diffuse large cell lymphomas (DLCLs), and 2 of 7 (29%) small noncleaved cell lymphomas (SNCs). Our analysis detected rearrangement of the 18q21 gene in 10 of 13 (77%) cases in which the t(14;18)(q32;q21) translocation was found by cytogenetic techniques. Our analysis also proved helpful in difficult karyotyping situations: (a) identifying the donor chromosome fragment as chromosome 18 band q21 in 4 of 9 (44%) cases that cytogenetically displayed a 14q+ chromosome of unknown origin, and (b) identifying a rearrangement of chromosome 18 band q21 in 12 of 18 (67%) cases that cytogenetically yielded no cells in metaphase. We also demonstrated three cases of submicroscopic rearrangement of the 18q21 gene. In our studies, patients with DLCLs and rearrangement of the 18q21 gene had a significantly higher incidence of extranodal involvement when compared with patients with DLCLs and no 18q21 gene rearrangement (P = 0.03).

Download Full-text