Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
International Journal of Hematology
Published in: International Journal of Hematology 5/2015

01-11-2015 | Progress in Hematology

Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia

Authors: Yoshikane Kikushige, Toshihiro Miyamoto

Published in: International Journal of Hematology | Issue 5/2015

Login to get access

Abstract

Human malignancies progress through a multistep process that includes the development of critical somatic mutations over the clinical course. Recent novel findings have indicated that hematopoietic stem cells (HSCs), which have the potential to self-renew and differentiate into multilineage hematopoietic cells, are an important cellular target for the accumulation of critical somatic mutations in hematological malignancies and play a central role in myeloid malignancy development. In contrast to myeloid malignancies, mature lymphoid malignancies, such as chronic lymphocytic leukemia (CLL), are thought to originate directly from differentiated mature lymphocytes; however, recent compelling data have shown that primitive HSCs and hematopoietic progenitor cells contribute to the pathogenesis of mature lymphoid malignancies. Several representative mutations of hematological malignancies have been identified within the HSCs of CLL and lymphoma patients, indicating that the self-renewing long-lived fraction of HSCs can serve as a reservoir for the development of oncogenic events. Novel mice models have been established as human mature lymphoma models, in which specific oncogenic events target the HSCs and immature progenitor cells. These data collectively suggest that HSCs can be the cellular target involved in the accumulation of oncogenic events in the pathogenesis of mature lymphoid and myeloid malignancies.
Literature
1.
Ding L, Ley TJ, Larson DE, Miller CA, Koboldt DC, Welch JS, et al. Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing. Nature. 2012;481(7382):506–10.PubMedCentralCrossRefPubMed
2.
Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K, et al. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med. 2012;366(12):1090–8.PubMedCentralCrossRefPubMed
3.
Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011;478(7367):64–9.CrossRefPubMed
4.
Wang L, Lawrence MS, Wan Y, Stojanov P, Sougnez C, Stevenson K, et al. SF3B1 and other novel cancer genes in chronic lymphocytic leukemia. N Engl J Med. 2011;365(26):2497–506.PubMedCentralCrossRefPubMed
5.
Puente XS, Pinyol M, Quesada V, Conde L, Ordonez GR, Villamor N, et al. Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia. Nature. 2011;475(7354):101–5.PubMedCentralCrossRefPubMed
6.
Quesada V, Conde L, Villamor N, Ordonez GR, Jares P, Bassaganyas L, et al. Exome sequencing identifies recurrent mutations of the splicing factor SF3B1 gene in chronic lymphocytic leukemia. Nat Genet. 2012;44(1):47–52.CrossRef
7.
Sakata-Yanagimoto M, Enami T, Yoshida K, Shiraishi Y, Ishii R, Miyake Y, et al. Somatic RHOA mutation in angioimmunoblastic T cell lymphoma. Nat Genet. 2014;46(2):171–5.CrossRefPubMed
8.
Morin RD, Mendez-Lago M, Mungall AJ, Goya R, Mungall KL, Corbett RD, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476(7360):298–303.PubMedCentralCrossRefPubMed
9.
Okosun J, Bodor C, Wang J, Araf S, Yang CY, Pan C, et al. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet. 2014;46(2):176–81.PubMedCentralCrossRefPubMed
10.
Landau DA, Carter SL, Stojanov P, McKenna A, Stevenson K, Lawrence MS, et al. Evolution and impact of subclonal mutations in chronic lymphocytic leukemia. Cell. 2013;152(4):714–26.PubMedCentralCrossRefPubMed
11.
Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, et al. Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms. Nature. 2009;460(7257):904–8.CrossRefPubMed
12.
Kato M, Sanada M, Kato I, Sato Y, Takita J, Takeuchi K, et al. Frequent inactivation of A20 in B-cell lymphomas. Nature. 2009;459(7247):712–6.CrossRefPubMed
13.
Morin RD, Johnson NA, Severson TM, Mungall AJ, An J, Goya R, et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet. 2010;42(2):181–5.PubMedCentralCrossRefPubMed
14.
Pasqualucci L, Dominguez-Sola D, Chiarenza A, Fabbri G, Grunn A, Trifonov V, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 2011;471(7337):189–95.PubMedCentralCrossRefPubMed
15.
Lenz G, Davis RE, Ngo VN, Lam L, George TC, Wright GW, et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science. 2008;319(5870):1676–9.CrossRefPubMed
16.
Palomero T, Couronne L, Khiabanian H, Kim MY, Ambesi-Impiombato A, Perez-Garcia A, et al. Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014;46(2):166–70.PubMedCentralCrossRefPubMed
17.
Oricchio E, Nanjangud G, Wolfe AL, Schatz JH, Mavrakis KJ, Jiang M, et al. The Eph-receptor A7 is a soluble tumor suppressor for follicular lymphoma. Cell. 2011;147(3):554–64.PubMedCentralCrossRefPubMed
18.
Lemonnier F, Couronne L, Parrens M, Jais JP, Travert M, Lamant L, et al. Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters. Blood. 2012;120(7):1466–9.CrossRefPubMed
19.
Cairns RA, Iqbal J, Lemonnier F, Kucuk C, de Leval L, Jais JP, et al. IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma. Blood. 2012;119(8):1901–3.PubMedCentralCrossRefPubMed
20.
Rossi DJ, Jamieson CH, Weissman IL. Stems cells and the pathways to aging and cancer. Cell. 2008;132(4):681–96.CrossRefPubMed
21.
Miyamoto T, Weissman IL, Akashi K. AML1/ETO-expressing nonleukemic stem cells in acute myelogenous leukemia with 8;21 chromosomal translocation. Proc Natl Acad Sci USA. 2000;97(13):7521–6.PubMedCentralCrossRefPubMed
22.
Miyamoto T, Nagafuji K, Akashi K, Harada M, Kyo T, Akashi T, et al. Persistence of multipotent progenitors expressing AML1/ETO transcripts in long-term remission patients with t(8;21) acute myelogenous leukemia. Blood. 1996;87(11):4789–96.PubMed
23.
Shima T, Miyamoto T, Kikushige Y, Yuda J, Tochigi T, Yoshimoto G, et al. The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell. Exp Hematol. 2014.
24.
Jan M, Snyder TM, Corces-Zimmerman MR, Vyas P, Weissman IL, Quake SR, et al. Clonal evolution of preleukemic hematopoietic stem cells precedes human acute myeloid leukemia. Sci Transl Med. 2012;4(149):149ra18.CrossRef
25.
Shlush LI, Zandi S, Mitchell A, Chen WC, Brandwein JM, Gupta V, et al. Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia. Nature. 2014;506(7488):328–33.CrossRefPubMed
26.
Welch JS, Ley TJ, Link DC, Miller CA, Larson DE, Koboldt DC, et al. The origin and evolution of mutations in acute myeloid leukemia. Cell. 2012;150(2):264–78.PubMedCentralCrossRefPubMed
27.
Walter MJ, Ding L, Shen D, Shao J, Grillot M, McLellan M, et al. Recurrent DNMT3A mutations in patients with myelodysplastic syndromes. Leukemia. 2011;25(7):1153–8.PubMedCentralCrossRefPubMed
28.
Kikushige Y, Ishikawa F, Miyamoto T, Shima T, Urata S, Yoshimoto G, et al. Self-renewing hematopoietic stem cell is the primary target in pathogenesis of human chronic lymphocytic leukemia. Cancer Cell. 2011;20(2):246–59.CrossRefPubMed
29.
Kikushige Y, Miyamoto T. Hematopoietic stem cell aging and chronic lymphocytic leukemia pathogenesis. Int J Hematol. 2014;100(4):335–40.CrossRefPubMed
30.
Quivoron C, Couronne L, Della Valle V, Lopez CK, Plo I, Wagner-Ballon O, et al. TET2 inactivation results in pleiotropic hematopoietic abnormalities in mouse and is a recurrent event during human lymphomagenesis. Cancer Cell. 2011;20(1):25–38.CrossRefPubMed
31.
Couronne L, Bastard C, Bernard OA. TET2 and DNMT3A mutations in human T-cell lymphoma. N Engl J Med. 2012;366(1):95–6.CrossRefPubMed
32.
Weigert O, Weinstock DM. The evolving contribution of hematopoietic progenitor cells to lymphomagenesis. Blood. 2012;120(13):2553–61.CrossRefPubMed
33.
Chung SS, Kim E, Park JH, Chung YR, Lito P, Teruya-Feldstein J, et al. Hematopoietic stem cell origin of BRAFV600E mutations in hairy cell leukemia. Sci Transl Med. 2014;6(238):238ra71.PubMedCentralCrossRefPubMed
34.
Chiorazzi N, Rai KR, Ferrarini M. Chronic lymphocytic leukemia. N Engl J Med. 2005;352(8):804–15.CrossRefPubMed
35.
Zenz T, Mertens D, Kuppers R, Dohner H, Stilgenbauer S. From pathogenesis to treatment of chronic lymphocytic leukaemia. Nat Rev Cancer. 2011;10(1):37–50.
36.
Stevenson FK, Caligaris-Cappio F. Chronic lymphocytic leukemia: revelations from the B-cell receptor. Blood. 2004;103(12):4389–95.CrossRefPubMed
37.
Caligaris-Cappio F, Ghia P. Novel insights in chronic lymphocytic leukemia: are we getting closer to understanding the pathogenesis of the disease? J Clin Oncol. 2008;26(27):4497–503.CrossRefPubMed
38.
Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V(H) genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848–54.PubMed
39.
Seifert M, Sellmann L, Bloehdorn J, Wein F, Stilgenbauer S, Durig J, et al. Cellular origin and pathophysiology of chronic lymphocytic leukemia. J Exp Med. 2012;209(12):2183–98.PubMedCentralCrossRefPubMed
40.
Sanchez ML, Almeida J, Gonzalez D, Gonzalez M, Garcia-Marcos MA, Balanzategui A, et al. Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone. Blood. 2003;102(8):2994–3002.CrossRefPubMed
41.
Landgren O, Albitar M, Ma W, Abbasi F, Hayes RB, Ghia P, et al. B-cell clones as early markers for chronic lymphocytic leukemia. N Engl J Med. 2009;360(7):659–67.CrossRefPubMed
42.
Marti GE, Rawstron AC, Ghia P, Hillmen P, Houlston RS, Kay N, et al. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol. 2005;130(3):325–32.CrossRefPubMed
43.
Nieto WG, Almeida J, Romero A, Teodosio C, Lopez A, Henriques AF, et al. Increased frequency (12 %) of circulating chronic lymphocytic leukemia-like B-cell clones in healthy subjects using a highly sensitive multicolor flow cytometry approach. Blood. 2009;114(1):33–7.CrossRefPubMed
44.
Dagklis A, Fazi C, Sala C, Cantarelli V, Scielzo C, Massacane R, et al. The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis is different from CLL: diagnostic implications for clinical monitoring. Blood. 2009;114(1):26–32.CrossRefPubMed
45.
Lanasa MC, Allgood SD, Volkheimer AD, Gockerman JP, Whitesides JF, Goodman BK, et al. Single-cell analysis reveals oligoclonality among ‘low-count’ monoclonal B-cell lymphocytosis. Leukemia. 2010;24(1):133–40.PubMedCentralCrossRefPubMed
46.
Shim YK, Rachel JM, Ghia P, Boren J, Abbasi F, Dagklis A, et al. Monoclonal B-cell lymphocytosis in healthy blood donors: an unexpectedly common finding. Blood. 2014;123(9):1319–26.PubMedCentralCrossRefPubMed
47.
Rawstron AC, Bennett FL, O’Connor SJ, Kwok M, Fenton JA, Plummer M, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008;359(6):575–83.CrossRefPubMed
48.
Marti G, Abbasi F, Raveche E, Rawstron AC, Ghia P, Aurran T, et al. Overview of monoclonal B-cell lymphocytosis. Br J Haematol. 2007;139(5):701–8.CrossRefPubMed
49.
Shanafelt TD, Kay NE, Rabe KG, Call TG, Zent CS, Maddocks K, et al. Brief report: natural history of individuals with clinically recognized monoclonal B-cell lymphocytosis compared with patients with Rai 0 chronic lymphocytic leukemia. J Clin Oncol. 2009;27(24):3959–63.PubMedCentralCrossRefPubMed
50.
Ghiotto F, Fais F, Valetto A, Albesiano E, Hashimoto S, Dono M, et al. Remarkably similar antigen receptors among a subset of patients with chronic lymphocytic leukemia. J Clin Invest. 2004;113(7):1008–16.PubMedCentralCrossRefPubMed
51.
Messmer BT, Albesiano E, Efremov DG, Ghiotto F, Allen SL, Kolitz J, et al. Multiple distinct sets of stereotyped antigen receptors indicate a role for antigen in promoting chronic lymphocytic leukemia. J Exp Med. 2004;200(4):519–25.PubMedCentralCrossRefPubMed
52.
Tobin G, Thunberg U, Karlsson K, Murray F, Laurell A, Willander K, et al. Subsets with restricted immunoglobulin gene rearrangement features indicate a role for antigen selection in the development of chronic lymphocytic leukemia. Blood. 2004;104(9):2879–85.CrossRefPubMed
53.
Widhopf GF 2nd, Rassenti LZ, Toy TL, Gribben JG, Wierda WG, Kipps TJ. Chronic lymphocytic leukemia B cells of more than 1 % of patients express virtually identical immunoglobulins. Blood. 2004;104(8):2499–504.CrossRefPubMed
54.
Sthoeger ZM, Wakai M, Tse DB, Vinciguerra VP, Allen SL, Budman DR, et al. Production of autoantibodies by CD5-expressing B lymphocytes from patients with chronic lymphocytic leukemia. J Exp Med. 1989;169(1):255–68.CrossRefPubMed
55.
Broker BM, Klajman A, Youinou P, Jouquan J, Worman CP, Murphy J, et al. Chronic lymphocytic leukemic (CLL) cells secrete multispecific autoantibodies. J Autoimmun. 1988;1(5):469–81.CrossRefPubMed
56.
Borche L, Lim A, Binet JL, Dighiero G. Evidence that chronic lymphocytic leukemia B lymphocytes are frequently committed to production of natural autoantibodies. Blood. 1990;76(3):562–9.PubMed
57.
Herve M, Xu K, Ng YS, Wardemann H, Albesiano E, Messmer BT, et al. Unmutated and mutated chronic lymphocytic leukemias derive from self-reactive B cell precursors despite expressing different antibody reactivity. J Clin Invest. 2005;115(6):1636–43.PubMedCentralCrossRefPubMed
58.
Bonnet D, Dick JE. Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med. 1997;3(7):730–7.CrossRefPubMed
59.
Akashi K, He X, Chen J, Iwasaki H, Niu C, Steenhard B, et al. Transcriptional accessibility for genes of multiple tissues and hematopoietic lineages is hierarchically controlled during early hematopoiesis. Blood. 2003;101(2):383–9.CrossRefPubMed
60.
Miyamoto T, Iwasaki H, Reizis B, Ye M, Graf T, Weissman IL, et al. Myeloid or lymphoid promiscuity as a critical step in hematopoietic lineage commitment. Dev Cell. 2002;3(1):137–47.CrossRefPubMed
61.
Damm F, Mylonas E, Cosson A, Yoshida K, Della Valle V, Mouly E, et al. Acquired initiating mutations in early hematopoietic cells of CLL patients. Cancer Discov. 2014;4(9):1088–101.CrossRefPubMed
62.
Vicente-Duenas C, Fontan L, Gonzalez-Herrero I, Romero-Camarero I, Segura V, Aznar MA, et al. Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice. Proc Natl Acad Sci USA. 2012;109(26):10534–9.PubMedCentralCrossRefPubMed
63.
Vicente-Duenas C, Romero-Camarero I, Gonzalez-Herrero I, Alonso-Escudero E, Abollo-Jimenez F, Jiang X, et al. A novel molecular mechanism involved in multiple myeloma development revealed by targeting MafB to haematopoietic progenitors. EMBO J. 2012;31(18):3704–17.PubMedCentralCrossRefPubMed
64.
Romero-Camarero I, Jiang X, Natkunam Y, Lu X, Vicente-Duenas C, Gonzalez-Herrero I, et al. Germinal centre protein HGAL promotes lymphoid hyperplasia and amyloidosis via BCR-mediated Syk activation. Nat Commun. 2013;4:1338.PubMedCentralCrossRefPubMed
65.
Green MR, Vicente-Duenas C, Romero-Camarero I, Long Liu C, Dai B, Gonzalez-Herrero I, et al. Transient expression of Bcl6 is sufficient for oncogenic function and induction of mature B-cell lymphoma. Nat Commun. 2014;5:3904.PubMedCentralCrossRefPubMed
Metadata
Title
Pre-malignant lymphoid cells arise from hematopoietic stem/progenitor cells in chronic lymphocytic leukemia
Authors
Yoshikane Kikushige
Toshihiro Miyamoto
Publication date
01-11-2015
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 5/2015
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-015-1740-1

Other articles of this Issue 5/2015

International Journal of Hematology 5/2015 Go to the issue

Erratum

Erratum to: A new transcriptional variant and small azurophilic granules in an acute promyelocytic leukemia case with NPM1/RARA fusion gene

Original Article

Absolute lymphocyte count at the end of induction therapy is a prognostic factor in childhood acute lymphoblastic leukemia

Case Report

Imatinib-induced gastric antral vascular ectasia in three patients with chronic myeloid leukaemia

Original Article

Rapamycin restores p14, p15 and p57 expression and inhibits the mTOR/p70S6K pathway in acute lymphoblastic leukemia cells

Original Article

Distribution of mutations in DNMT3A gene and the suitability of mutations in R882 codon for MRD monitoring in patients with AML

Images in Hematology

Bilateral psoas muscle lymphoma: an unusual presentation of EBV-positive diffuse large B-cell lymphoma of the elderly
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits