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The cells of origin of these small B\u2010cell lymphomas are distinct, as are the characteristic chromosomal lesions and clinical courses. One shared feature is retention of expression of surface immunoglobulin. Analysis of this critical receptor reveals the point of differentiation reached by the cell of origin. Additionally, the sequence patterns of the immunoglobulin\u2010variable domains can indicate a role for stimulants of the B\u2010cell receptor before, during and after malignant transformation. The pathways driven via the B\u2010cell receptor are now being targeted by specific kinase inhibitors with exciting clinical effects. To consider routes to pathogenesis, potentially offering earlier intervention, or to identify causative factors, genetic tools are being used to track pretransformation events and the early phases in lymphomagenesis. These methods are revealing that chromosomal changes are only one of the many steps involved, and that the influence of surrounding cells, probably multiple and variable according to tissue location, is required, both to establish tumours and to maintain growth and survival. Similarly, the influence of the tumour microenvironment may protect malignant cells from eradication by treatment, and the resulting minimal residual disease will eventually give rise to relapse. The common and different features of the four lymphomas will be summarized to show how normal B lymphocytes can be subverted to generate tumours, how these tumours evolve and how their weaknesses can be attacked by targeted therapies.<\/jats:p>","DOI":"10.1111\/joim.12608","type":"journal-article","created":{"date-parts":[[2017,4,10]],"date-time":"2017-04-10T05:48:48Z","timestamp":1491803328000},"page":"395-414","source":"Crossref","is-referenced-by-count":8,"title":["Early stages in the ontogeny of small B\u2010cell lymphomas: genetics and microenvironment"],"prefix":"10.1111","volume":"282","author":[{"given":"P.","family":"Ghia","sequence":"first","affiliation":[{"name":"Division of Experimental Oncology Universit\u00e0 Vita\u2010Salute San Raffaele and IRCCS San Raffaele Scientific Institute Milan Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Nadel","sequence":"additional","affiliation":[{"name":"Aix\u2010Marseille Universit\u00e9 CNRS INSERM CIML Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B.","family":"Sander","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Division of Pathology Karolinska Institutet and Karolinska University Hospital Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K.","family":"Stamatopoulos","sequence":"additional","affiliation":[{"name":"Institute of Applied Biosciences Center for Research and Technology Hellas Thessaloniki Greece"},{"name":"Department of Immunology, Genetics and Pathology Science for Life Laboratory Uppsala University Uppsala Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"F. 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