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Waldenstro¨M's Macroglobulinemia Is a Biological Syndrome Which May

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Waldenstro¨M's Macroglobulinemia Is a Biological Syndrome Which May Correspondence 1637 cation,10 particularly in acute promyelocytic leukemia (APL), we References searched for genomic similarities. The few specific studies in existence on sequence analysis of the PML-RAR␣ gene show that the breakpoint within the involved gene (usually the PML locus) is variably situated, 1 Saglio G, Guerrasio A, Tassinari A, Ponzetto C, Zaccaria A, Testoni and that the corresponding fusion transcript should be aberrant. The P, Celso B, Rege Cambrin G, Serra A, Pegoraro L. Variability of the ␣ resulting PML-RAR proteins contained residues not homologous with molecular defects corresponding to the presence of a Philadelphia ␣ either PML or RAR . These reported atypical breaks were very similar chromosome in human hematologic malignancies. Blood 1988; to the one recorded in our case. A second original characteristic of 72: 1203–1208. the BCR break reported by us is that an intronic sequence derived 2 Chissoe SL, Bodenteich A, Wang YF, Wang YP, Burian D, Clifton from abl intron Ib was juxtaposed to bcr exon. This is another unpre- SW, Crabtree J, Freeman A, Iyer K, Jian L. Sequence and analysis cedented feature for a CML patient, although on rare occasions it has 10 of the human ABL gene, the BCR gene, and regions involved in been reported in AML patients. So, it may be speculated that in a the Philadelphia chromosomal translocation. Genomics 1995; 27: small proportion of the DNA breaks that occurs in leukemia, a cur- 67–82. rently unknown molecular mechanism could break the coding DNA. 3 Saglio G, Guerrasio A, Rosso C, Zaccaria A, Tassinari A, Serra A, The resulting RNA remains in-frame coding an aberrant or, as in our Rege-Cambrin G, Mazza U, Gavosto F. New type of Bcr/Abl junc- case, variant oncogenic protein. The involvement of the Translin pro- tein or Translin related protein (TRAX)8 in the generation of our cases tion in Philadelphia chromosome-positive chronic myelogenous is strongly supported by the fact that homology sequences were leukemia. Blood 1990; 76: 1819–1824. present on both sides of the genes involved in the rearrangement. 4 Pane F, Frigeri F, Sindona M, Luciano L, Ferrara F, Cimino R, These observations support the hypothesis that the role of Translin Meloni G, Saglio G, Salvatore F, Rotoli B. Neutrophilic-chronic could be more important in CML patients translocation than in other myeloid leukemia: a distinct disease with a specific molecular non-lymphoid leukemia-associated rearrangements. market (BCR/ABL with C3/A2 junction). Blood 1996; 88: 2410– 2414. 5 Testoni N, Martinelli G, Farabegoli P, Zaccaria A, Amabile M, Raspadori D, Pelliconi S, Zuffa E, Carboni C, Tura S. A new Acknowledgements method of ‘in cell RT-PCR’ for the detection of bcr-abl transcript in chronic myeloid leukemia patients. Blood 1996; 87: 3822–3827. This work was supported by Italian Association of Cancer 6 Saglio G, Pane F, Gottardi E, Frigeri F, Buonaiuto MR, Guerrasio Research (AIRC), by Italian CNR No. 98.00526.CT04 target A, de Micheli D, Parziale A, Fornaci MN, Martinelli G, Salvatore projects, by ‘30 Ore per la Vita’ AIL grants and by MURST F. Consistent amounts of acute leukemia-associated P190BCR/ABL 40% project. The authors are grateful to Prof Pier Giuseppe transcripts are expressed by chronic myelogenous leukemia Pelicci for helpful discussion on results and to Mr Robin MT patients at diagnosis. Blood 1996; 87: 1075–1080. Cooke for editorial assistance. 7 Pearson WR. Rapid and sensitive sequence comparison with FASTP and FASTA. Meth Enzymol 1990; 183: 63–98. 11 8 Aoki K, Ishida R, Kasai M. Isolation and characterization of a G Martinelli Institute of Hematology and cDNA encoding a Translin-like protein, TRAX. FEBS Lett 1997; 1 C Terragna Medical Oncology ‘Sera`gnoli’, 401: 109–112. M Amabile1 University of Bologna; and 9 Selleri L, Narni F, Emilia G, Colo` A, Zucchini P, Venturelli D, V Montefusco12Department of Biomedical Science Donelli A, Torelli U, Torelli G. Philadelphia-positive chronic N Testoni1 and Human Oncology, University myeloid leukemia with a chromosome 22 breakpoint outside the E Ottaviani1 of Turin, Italy breakpoint cluster region. Blood 1987; 70: 1659–1664. A de Vivo1 10 Gallagher RE, Li YP, Rao S, Paietta E, Andersen J, Etkind P, Bennett 1 JM, Tallman MS, Wiernik PH. Characterization of acute promyelo- A Mianulli cytic leukemia cases with PML-RAR␣ break/fusion sites in PML E Trabacchi exon 6: identification of a subgroup with decreased in vitro G Saglio2 responsiveness to all-trans retinoic acid. Blood 1995; 86: 1540– S Tura1 1547. Waldenstro¨m’s macroglobulinemia is a biological syndrome which may occur during the evolution of different types of low grade B cell lymphoma TO THE EDITOR plasmacytoid lymphocytes with a high level of circulating macroglob- ulin IgM.2 The seric level of the IgM component should be over 5 g/l. The cases reported in the letter sent by Allez et al1 demonstrate that Lymphadenopathy and splenomegaly occur in 20–40% of cases while Waldenstro¨m’s macroglobulinemia (WM) can occur in low grade Malt gastrointestinal involvement has been reported in about 5–10% of lymphoma when disseminated. This is also our experience but in cases. addition, WM may be observed in association with different other It is now well demonstrated that different types of small B cell lym- small B cell lymphomas. phomas may comprise a lympho-plasmacytoid/lymphoplasmacytic The accepted definition of MW is that given by Brouet et al2 in component. Immunohistochemistry demonstrates the presence of 1975. This disease is defined as bone marrow infiltration by lympho- monotypic immunoglobulin in the cytoplasm, in the perinuclear cis- ternae and sometimes in expansion of this cisternae realizing intranu- clear vacuoles3 described by Dutcher and Fahey.4 These vacuoles can also be disclosed by PAS staining, when the heavy chain is of the Correspondence: J Diebold, Service Central ‘Jacques-Delarue’ d’Ana- mu type. tomie et de Cytologie Pathologiques, Hoˆpital Hoˆtel-Dieu de Paris, 1, At least three different types of small B cell lymphomas other than Place du Parvis de Notre-Dame, 75181 Paris Cedex 04, France; lymphoplasmacytic lymphoma can be associated with a WM presen- Fax: 33 1 42 34 86 41 tation. Received 12 May 1999; accepted 8 June 1999 (1) Disseminated forms of gastro-intestinal low-grade MALT lym- phoma have been well documented by Allez et al.1 Correspondence 1638 (2) B-CLL with lymphoplasmacytoid differentiation represents another splenic marginal zone lymphoma and nodal monocytoid B cell lym- example. phoma on the one hand, and B-CLL with a lymphoplasmacytoid This variant of B-CLL accepted in the new WHO classification differentiation on the other hand. which is in progress,5 corresponds to the lympho-plasmacytoid type of immunocytoma described in the up-dated Kiel classi- J Diebold Service central 6 fication based on the proposals of K Lennert distinguishing two T Molina ‘Jacques-Delarue’ d’Anatomie et de subtypes of immunocytomas, the lymphoplasmacytoid and the F Tissier Cytologie Pathologique, lymphoplasmacytic. One of us (JD) reported many years ago such A le Tourneau Hoˆtel-Dieu, Paris, France a case, which transformed 5 years after publication into a J Audouin typical WM.7 (3) primary splenic marginal zone lymphoma represents another example of such an association. We are now reporting a series of 31 cases of this type of lymphoma.8 A lymphoplasmacytic compo- References nent secreting intra-cytoplasmic monotypic immunoglobulins has been demonstrated by immunohistochemistry on frozen and/or 1 Allez M, Mariette X, Linares G, Bertheau P, Jian R, Brouet JC. Low- paraffin embedded tissue in 23 cases. In all cases which had an grade MALT lymphoma mimicking Waldenstro¨m’s macroglobuline- iliac crest trephine biopsy, the bone marrow was involved by the mia. Leukemia 1999; 13: 484–485. same immunoglobulin secreting lymphoplasmacytic component. 2 Brouet JC, Clauvel JP, Seligmann M. Evolution et pronostic de la For eight cases, out of these 23, we had no information about the maladie de Waldenstro¨m. Etude de 150 observations. Actualite´s presence or absence of seric monoclonal component. Four cases He´matologiques. Masson et cie. Paris 1975; 9: 38–47. had no seric spike. In four patients, a minimal seric monoclonal 3 Diebold J, Reyne`s M, Kalifat R, Tricot G. Les inclusions intra-nucle´- component was present, less than 5 g/l. But in seven cases with aires de la maladie de Waldenstro¨m. Significant biologique et val- a seric monoclonal component higher than 5 g/l, the diagnosis of eur diagnostique. Nouv Presse Med 1974; 3: 1067–1070. MW has been proposed. Eleven patients of this group also had 4 Dutcher TF, Fahey JL. The histopathology of the macroglobulinemia auto-immune disorders, particularly auto-immune hemolytic of Waldenstro¨m. J Natl Cancer Inst 1959; 22: 887–917. anaemia. 5 Jaffe ES, Harris NL, Diebold J, Mu¨ller-Hermelink HK. World Health Organization classification of neoplastic diseases of the hematopo- The eight patients without such a lymphoplasmacytic cell compo- ietic and lymphoid tissues: a progress report. Am J Clin Pathol 1999; nent in the spleen had no seric monoclonal immunoglobulin, and no 111 (Suppl.): S8–S12. auto-immune disorders. 6 Stansfeld AG, Diebold J, Kapanci Y, Kelenyi G, Lennert K, Mlo- In addition, we have disclosed a lymphoplasmacytic cell compo- duszewska O, Noel H, Rilke F, Sundstro¨m C, Vaunnik JAM, Wright nent producing a monotypic immunoglobulin in nodal monocytoid B DH. Up-dated Kiel classification for lymphomas. Lancet 1988; i: cell lymphoma and even in one case of follicular B cell ML with mar- 292–293 and 603. ginal zone differentiation. These lymphomas may also perhaps be 7 Diebold J, Zittoun R, Fine JM, Tricot G, Camilleri JP, Simon F, Alca- responsible in a few number of patients for such a WM.
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