Chronic lymphocytic leukemia with two cellular populations: a biphenotypic or biclonal disease

Abstract

A case of CLL with two different cellular populations is reported. A 50-year-old man was evaluated for persistent absolute lymphocytosis. A peripheral blood smear revealed numerous small lymphocytes (83% of white blood cells counted). Frequent Grumpecht shadows were present, too. On bone marrow aspirate smears lymphocytes comprised 85% of the total cells counted, and the bone marrow biopsy showed a mixed nodular-interstitial infiltration pattern. The immunophenotypic study showed two different leukemic populations. The first one (comprising 79% leukemic cells) was CD5+, CD19+, CD10-, CD20+, CD18-, CD22-, CD23+ +, lambda dim, and FMC7-. The second population (comprising 21% leukemic cells) was CD5+, CD19+, CD10-, CD20+, CD18+, CD22+, CD23+, lambda+ +, and FMC7+. Gene rearrangement studies detected the germline and one rearranged band in Jk blot with each restriction endonuclease. In the Jh blot the germline and two rearranged bands were detected with EcoRI and BamHI and three rearranged bands with HindIII. The JBI/JBII blot detected only the germline band. The detection of three rearranged bands was interpreted as evidence of the presence of at least two monoclonal populations of cells with the same light chain restriction.

Incidence and clinicobiologic characteristics of leukemic B-cell chronic lymphoproliferative disorders with more than one B-cell clone

“…Previous case reports on biclonal CLPD have suggested the existence of large phenotypic differences between the 2 expanded cell clones. 15,17,19 In the present study, a detailed analysis of the phenotypic differences between the coexisting neoplastic cell clones showed that they are relatively variable from one diagnostic subgroup to another, and cases existed in which the phenotypic differences between clones were restricted to a single marker, together with patients displaying more complex phenotypic patterns. Virtually all antigens analyzed were found to be differentially expressed in the 2 coexisting B-cell clones.…”

“…1 In fact, in B-CLPD oligoclonality has been usually related to the development of new B-cell subclones resulting from the occurrence of additional genetic abnormalities on the neoplastic cells along the evolution of the disease [29][30] ; reports on B-CLPD cases with 2 or more distinct unrelated B-cell clones are scanty in the literature and restricted to between 1 and 3 patients at maximum. 12,15,[17][18][19]31,32 In most of these cases, biclonality was suspected based on flow cytometry immunophenotypic studies, which revealed the presence of 2 phenotypically distinct B-cell populations, 15,17 frequently displaying a different sIg light chain isotype 12,17,18,31,32 ; molecular analysis confirmed the presence of 2 unrelated malignant clones, indicating that these cases corresponded to true biclonal B-CLPD. 12,[15][16][17]31,32 Nevertheless, until now the incidence of biclonality among B-CLPD has not been established.…”

“…12,15,[17][18][19]31,32 In most of these cases, biclonality was suspected based on flow cytometry immunophenotypic studies, which revealed the presence of 2 phenotypically distinct B-cell populations, 15,17 frequently displaying a different sIg light chain isotype 12,17,18,31,32 ; molecular analysis confirmed the presence of 2 unrelated malignant clones, indicating that these cases corresponded to true biclonal B-CLPD. 12,[15][16][17]31,32 Nevertheless, until now the incidence of biclonality among B-CLPD has not been established. The first goal of the present study was to determine this incidence; for that purpose, we have analyzed at diagnosis a large series of 477 consecutive patients suffering from leukemic B-CLPD.…”

“…In this sense, the presence of 2 or more morphologically different populations of neoplastic lymphocytes in the same patient, detected either simultaneously or at different time points, is usually interpreted as reflecting either different maturation stages or subclone formation within the original malignant tumor stem cell line. 7 Although most lymphoproliferative disorders are considered to be monoclonal, biclonality has been occasionally reported in the literature, [8][9][10][11][12][13][14][15][16][17][18][19] frequently corresponding to rare cases of B-cell nonHodgkin lymphomas (NHLs), which more commonly develop in immunocompromised individuals. [8][9][10][11] In most instances these reports describe the coexistence of 2 distinct diseases such as mantle cell lymphoma (MCL) and follicular lymphoma (FL), 17 FL and small lymphocytic lymphoma (SLL), 17 MCL and chronic lymphocytic leukemia/SLL (CLL/SLL), 17 SLL and large cell lymphoma (LCL), 18 and hairy cell leukemia (HCL) and CLL/SLL.…”

Double productive immunoglobulin sequence rearrangements in patients with chronic lymphocytic leukemia

“…The expression of a single Ig light chain by CLL B-cells (j or k) was required ( Fig. 1) based on previous studies reporting that biclonality in CLL can be reliably ascertained by flow cytometry, with distinct B-cell populations usually expressing different sIg light chains isotypes [9,36,40,41]. To confirm this assumption in our series, we studied two cases with double IGHV rearrangement where flow cytometry had revealed expression of distinct surface Ig light chain (j and k).…”