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Pathobiology of B-Lymphoproliferative Disorders: From MBL to CLL and SLL (CROSBI ID 48467)

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Dominis, Mara ; Korać, Petra ; Ajduković Radmila Pathobiology of B-Lymphoproliferative Disorders: From MBL to CLL and SLL // Horizons in cancer research, Volume 52 / Watanabe, Hiroto S. (ur.). New York (NY): Nova Science Publishers, 2013. str. 115-139

Podaci o odgovornosti

Dominis, Mara ; Korać, Petra ; Ajduković Radmila

engleski

Pathobiology of B-Lymphoproliferative Disorders: From MBL to CLL and SLL

Chronic lymphocytic leukemia (CLL) consists of a heterogeneous cell population, originating from B- cells between pre-B and mature B-cell developmental stages. Tumor cells are non- functional B lymphocytes with the phenotype CD19+CD5+ CD23+ that accumulate in bone marrow and cause lymphocytosis. CLL can be preceded by and/or mistaken for monoclonal B-cell lymphocytosis (MBL) or it can be found in lymph nodes, where the same cells form small lymphocytic lymphoma (SLL). In rare cases, it can transform into a diffuse large B-cell lymphoma called Richter’s syndrome. There are two main subgroups of CLL with different prognostic impact. One subgroup has a mutated IgVH gene (M-CLL) and shows much longer survival, while the other has an unmutated IgVH gene (U-CLL) which is used as a mark of poor prognosis. There are also some other known prognostic markers: trisomy 12, del 17p, del 11p, del 13q14.3, del 6q21, expression of ZAP-70 or CD38 by tumor cells as well as many other frequently emerging single markers. Those factors serve as prognostic variables in classical CLL while a relatively small proportion of similar markers for MBL or SLL have been identified so far. Beside tumor cell genetics, epigenetic regulation of transcription within neoplastic cells and studies about tumor microenvironment suggesting that CLL cells respond to microenvironmental signals which can extend survival and cause transformation of CLL cells can hopefully improve our understanding of evolution of this neoplasm. Premalignant stage, MBL, has to be provoked in order to subdue further oncogenic changes and progress to CLL. In the case of SLL, events suppressing leukemic presentation must be a significant step in its pathogenesis as well as aberrations that constitute starting point of the transformation to Richter’s syndrome. This chapter gives an overview of the following topics: proposed developmental pathways of CLL, morphological criteria for the diagnosis of MBL/CLL/SLL/Richter’s syndrome, immunohistochemical markers, genetic alterations, and BCR signaling pathway in both MBL and CLL, algorithms for assessment of MBL patients in order to distinguish the group that will eventually develop CLL, and update of prognostic factors in the current clinical practice.

MBL, CLL, SLL, diagnosis, prognostic markers, treatment

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Podaci o prilogu

115-139.

objavljeno

Podaci o knjizi

Horizons in cancer research, Volume 52

Watanabe, Hiroto S.

New York (NY): Nova Science Publishers

2013.

978-1-62808-046-9

Povezanost rada

Temeljne medicinske znanosti, Kliničke medicinske znanosti, Biologija