Leukemic phase of B-lineage NHL
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
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| Zitieren: | Leukemic phase of B-lineage NHL / E. Kimby // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 384-385. — Бібліогр.: 14 назв. — англ. |
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irk-123456789-1398552018-06-22T03:05:45Z Leukemic phase of B-lineage NHL Kimby, E. Conference reports 2012 Article Leukemic phase of B-lineage NHL / E. Kimby // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 384-385. — Бібліогр.: 14 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/139855 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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Conference reports Conference reports |
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Conference reports Conference reports Kimby, E. Leukemic phase of B-lineage NHL Experimental Oncology |
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Article |
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Kimby, E. |
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Kimby, E. |
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Kimby, E. |
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Leukemic phase of B-lineage NHL |
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Leukemic phase of B-lineage NHL |
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Leukemic phase of B-lineage NHL |
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Leukemic phase of B-lineage NHL |
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Leukemic phase of B-lineage NHL |
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leukemic phase of b-lineage nhl |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
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2012 |
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Conference reports |
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http://dspace.nbuv.gov.ua/handle/123456789/139855 |
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Leukemic phase of B-lineage NHL / E. Kimby // Experimental Oncology. — 2012. — Т. 34, № 4. — С. 384-385. — Бібліогр.: 14 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT kimbye leukemicphaseofblineagenhl |
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2025-07-10T09:14:20Z |
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2025-07-10T09:14:20Z |
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1837250763657576448 |
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��� Experimental Oncology ��� �������� ���� ��ecem�er�
2. Cesarman E. Gammaherpesvirus and lymphoprolifera-
tive disorders in immunocompromised patients. Cancer Lett
2011; 305: 163–74.
3. Gaidano G, Capello D, Carbone A. The molecular basis
of acquired immunodeficiency syndrome-related lymphoma-
genesis. Semin Oncol 2000; 27: 431–41.
4. Gaidano G, Carbone A. Primary effusion lympho-
ma: a liquid phase lymphoma of fluid-filled body cavities. Adv
Cancer Res 2001; 80: 115–46.
5. Gantt S, Casper C. Human herpesvirus 8-associated
neoplasms: the roles of viral replication and antiviral treatment.
Curr Opin Infect Dis 2011; 24: 295–30l.
6. Marcucci F, Mele A. Hepatitis viruses and non-Hodgkin
lymphoma: epidemiology, mechanisms of tumorigenesis, and
therapeutic opportunities. Blood 2011; 17: 1792–8.
7. Michieli M, Mazzucato M, Tirelli U, De Paoli P. Stem
cell transplantation for lymphoma patients with HIV infection.
Cell Transplant 2011; 20: 351–70.
8. Ramos JC, Lossos IS. Newly emerging therapies target-
ing viral-related lymphomas. Curr Oncol Rep 2011; 3: 4l6–26.
9. Spina M, Gloghini A, Tirelli U, Carbone A. Therapeutic
options for HIV-associated lymphomas. Expert Opin Pharma-
cother. 2010; 11: 2471–81.
10. Yodoi J, Maeda M. Discovery of ATL: an odyssey
in restrospect. Int J Hematol 2011; 94: 423–8.
LEUKEMIC PHASE OF B-LINEAGE NHL
E. Kimby
Department of Hematology, Karolinska Institute
at Huddinge University Hospital
Stockholm S-141 86, Sweden
Correspondence: eva.kimby@swipnet.se
B-cell non-Hodgkin lymphomas �NHL� mostly pres-
ent as disseminated diseases involving lymph nodes�
spleen and liver and often the �one marrow �BM�.
Tumor cells can also �e found in the �lood �leukemic
disease�� especially in the indolent lymphomas. High
white �lood cell counts and a differential demonstra-
ting a lymphocytosis in the �lood require immunophe-
notyping for characterization of the leukemic cells.
Molecular/cytogenetic analyses may also have a role
in the diagnostic classification of the disease. Besides
the specific diagnosis� the clinical evaluation of the pa-
tient and prognostic markers are of most importance
for selecting the �est type of therapy.
Follicular lymphoma (FL) is the indolent lymphoma
with the highest incidence. Most patients present
with advanced stage disease with BM involvement
in �����% of the cases� and few are leukemic at the
time of diagnosis. By high-resolution analysis circulating
FL cells may �e detected in more patients. Leukemic pa-
tients mostly have concomitant lymph node involvement
and high tumor �urden. A pure FL-cell leukemia with
C���+C���+C�5� clonal cells has also �een descri�ed�
mostly associated with an indolent clinical outcome.
FL carry a t�l�;l���q��;q�l� translocation in more than
9�% of cases� juxtaposing the immunoglo�ulin heavy
chain �IGH� �’ Regulatory Regions �lgH-�’RR� to the
BCL2 gene� resulting in overexpression of the Bcl� anti-
apoptotic protein. FL cells are also dependent on signals
from the microenvironment to survive and proliferate.
Several groups� including ours� have reported that
immune cells in the lymphoma microenvironment and
in �lood influence prognosis. In patients treated �efore
the introduction of rituxima�� we have found that a high
num�er of P�-�+� FOXP�+ and C��+ T-cell su�sets in the
tumor microenvironment predict superior outcome�
while C��+ follicular helper T cells and C�6�+ macro-
phages are associated with an inferior outcome. The
introduction of the anti-C��� anti�ody rituxima� has
improved the prognosis for FL patients. The efficacy
of this drug is excellent also as monotherapy especially
in patients with high num�ers of C��+ T-cells in the
lymph nodes as well as in the �lood.
Mantle cell lymphoma (MCL): MCL cells carries
the t�l �:��� translocation resulting in enhanced cyclin
�l expression and cyclin �I-dependent kinase activ-
ity� promoting cell cycle progression. Immunological
markers show a typical phenotype �C���+C�5+C������
�ut also atypical phenotypes �C���+C�5�C����
or C���+C�5+C���+� in some cases. Most MCL patients
have an unfavora�le prognosis and intensive treatment
strategies are required. However� in around ��% of the
patients the disease shows an indolent clinical course
with often a non-nodal� leukemic disease. In one study
the clinicopathologic features� gene expression and
genomic profiles were compared in patients with in-
dolent �iMCL� and in those with conventional disease
�cMCL�. iMCL and cMCL shared a common gene
expression profile that differed from other leukemic
lymphoid neoplasms and a signature of �� genes was
underexpressed in iMCL� among these SOXI1. The SOX
I1-negative tumors exhi�ited more frequent non-nodal
presentation and �etter survival compared with SOX
I1-positive MCL. Recently� our group found that SOXII-
negative MCL had a higher frequency of lymphocytosis�
�ut also elevated L�H and p5� positivity. Moreover�
SOXII- negative cases had a shorter overall survival than
SOXII-positive cases. �ue to the conflicting results� the
conclusion is that SOXII cannot �e used for predicting
an indolent disease course. In another study� deletions
at ��p�� (TP53) and ��q�� were frequent in leukemic
MCL and involved the majority of the leukemic clone.
Cases with TP53 deletion were more likely to have
splenomegaly and marked leucocytosis �> �� × ��9/L��
and were less likely to have lymphadenopathy than
those without the deletion. Other distinctive �iological
features in non-nodal leukemic MCL are mutated IGHV
and a transcriptional profile lacking tumor invasion prop-
erties� which might contri�ute to the a�sence of nodal
involvement. In conclusion� MCL patients with leukemic
disease �ut without clinical symptoms might �e man-
aged conservatively with a “wait and watch” policy� while
�lastoid morphology� high proliferation and TP53 a�er-
rations are markers of aggressive disease� which will
require intensive immunochemotherapy.
Marginal zone lymphoma (MZL): There are three
clinicopathological entities of MZL� including extranod-
al� mucosa-associated lymphoid tissue �MALT� lympho-
ma� nodal �NMZL�� and splenic �SMZL� type. Leukemic
presentation is more common in SMZL. The leukemic
Experimental Oncology ��� �������� ���� ��ecem�er���� �������� ���� ��ecem�er� ��ecem�er� ��5
lymphocytes are usually small or morphologically “vil-
lous”� and the leukemic manifestation of SMZL is named
splenic lymphoma with villous lymphocytes �SLVL�. The
typical immunophenotype is C��9+C���+C���+C��5+
and the clone is often also C� ���+ and C���+. More-
over� C���c is highly associated with SMZL. The genet-
ics and pathogenesis of SMZL are poorly understood
and specific prognostic features are lacking. A�errant
karyotypes are seen as gains of �/�q and ��q� deletions
of �q and 6q and translocations involving �q/�q/l�q.
Trisomy � and deletions of chromosome �q��-�� are
most common and found in approximately �5 and �5%
of cases� respectively. A strong association has �een
descri�ed �etween usage of the IGVH�-� and deletion
�q and ��q alterations. Clinical and epidemiological
data suggest that chronic hepatitis C virus �HCV� infec-
tion may have an etiological role in a su�set of cases.
MicroRNA �miR�-�6�� a miRNA known to have tumor
suppressive properties� has �een shown to �e down-
regulated in HCV positive cases. Recent data suggest
that certain SMZL su�types could derive from progeni-
tor populations adapted to particular antigenic chal-
lenges through selection of VH domain specificities�
in particular the IGHV �-��*��� allele.
The anti-C��� anti�ody rituxima� is mostly ef-
fective in MZL patients as monotherapy� �ut for many
patients with symptomatic splenomegaly� splenectomy
is still a therapeutic option.
In summary� the presence of lymphocytosis in the
�lood in patients with a suspicion of lymphoma requires
careful evaluation for the presence of neoplastic lym-
phocytes� especially in the a�sence of easily acces-
si�le enlarged lymph nodes. The differential diagnosis
�etween the WHO defined mature B-cell malignancies
has improved �y using multiple-color flow cytometry
of phenotypic data of the lymphoma cells. This method
is also of value for characterization of the immune
cells in the microenvironment and �lood. Molecular/
cytogenetic analyses have a role in classification
of the disease and for understanding of pathogenesis.
Therapeutic decisions are always dependant on the
specific diagnosis� prognostic factors and a careful
clinical evaluation of the patient.
REFERENCES
1. Bene MC, Nebe T, Bettelheim P, et al. Immunophe-Immunophe-
notyping of acute leukemia and lymphoproliferative disor-
ders: a consensus proposal of the European LeukemiaNet
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2. Wahlin BE, Sundstrom C, Holte H, et al. T cells
in tumors and blood predict outcome in follicular lymphoma
treated with rituximab. Clin Cancer Res. 2011; 17: 4136–44
3. Matutes E, Parry-Jones N, Brito-Babapulle V, et al.
The leukemic presentation of mantle-cell lymphoma: disease
features and prognostic factors in 58 patients. Leuk Lymphoma
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4. Fernandez V, Salamero O, Espinet B, et al. Genomic
and gene expression profiling defines indolent forms of mantle
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5. Nygren L, Baumgartner Wennerholm S, et al. Prognostic
role of SOX I I in a population-based cohort of mantle cell
lymphoma. Blood 2012; 119: 4215–23.
6. Del Giudice I, Messina M, Chiaretti S, et al. Behind the
scenes of non-nodal MCL: downmodulation of genes involved
in actin cytoskeleton organization, cell projection, cell adhesion,
tumour invasion, TP53 pathway and mutated status of immu-
noglobulin heavy chain genes. J Haematol 2012; 156: 601–11.
7. Isaacson PG, Matutes E, Burke M, Catovsky D. The
histopathology of splenic lymphoma with villous lymphocytes.
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B-cell disorders. Blood 1994; 83: 1558–62.
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11. Parry-Jones N, Matutes E, Gruszka-Westwood AM, et al.
Prognostic features of splenic lymphoma with villous lympho-
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12. Del Giudice I, Matutes E, Morilla R, et al. The diag-The diag-
nostic value of CD 123 in B-cell disorders with hairy or villous
lymphocytes. Haematologica 2004; 89: 303–8.
13. Matutes E, Oscier D, Montalban C, et al. Splenic
marginal zone lymphoma proposals for a revision of diagnostic,
staging and therapeutic criteria. Leukemia 2008; 22: 487–95.
14. Salido M, Baro C, Oscier D, et al. Cytogenetic aber-Cytogenetic aber-
rations and their prognostic value in a series of 330 splenic
marginal zone B-cell lymphomas: a multicenter study of the
Splenic B-Cell Lymphoma Group. Blood 2010; 116: 1479–88.
PRIMARY GASTROINTESTINAL
LYMPHOMAS
E. Vandenberghe
Haematology/Oncology Day Care Centre, St.
James’s Hospital, Dublin, Ireland
Correspondence: vandenberghesec@stjames.ie
Epidemiology and classification
Primary gastrointestinal lymphomas comprise less
than 5% of all lymphomas diagnosed in the western
world� with a varia�le geographical and ethnic inci-
dence. The �iology and management vary with the
main diagnostic �WHO� su�types which include Gastric
MALT lymphomas� Enteropathy associated T-cell lym-
phoma �EATCL�. Other lymphomas which frequently
involve the gastrointestinal tract include diffuse large
B-cell lymphoma� mantle cell lymphoma and Burkitts
lymphoma; �ut are not considered primary gut lym-
phomas and will not �e covered in this lecture. The
pathogenesis of MALT and EATCL lymphomas is linked
to a�normal antigen drive �gluten/Helicobacter infec-
tion� resulting in chronic inflammation and lymphoma
development. The lymphomas are otherwise radically
different; MALT lymphomas are indolent B-NHL� which
respond to antigen-drive withdrawal and minimal
therapy with an overall survival �OS� > ��% at 5 years�
whereas EATCL is an aggressive T-cell lymphomas
associated with a poor outcome.
Gastric MALT lymphoma
Clinical features: Gastric MALT lymphomas in-
cidence in the Western World is approximately 6 per
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