Improved Detection of Chromosomal Abnormalities in CLL by Conventional Cytogenetics Using CpG Oligonucleotide and Interleukin-2 Stimulation. A Belgian Multicentric Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3118-3118
Author(s):  
Natalie Put ◽  
Katrina Rack ◽  
Nadine Van Roy ◽  
Jeanne-Marie Libouton ◽  
Pascal Vannuffel ◽  
...  
Keyword(s):  
B Cell ◽  
Mitotic Index ◽  
Cytogenetic Analysis ◽  
Detection Rate ◽  
Interleukin 2 ◽  
Fish Analysis ◽  
Specific Change ◽  
Interphase Fish ◽  
Cpg Oligonucleotide ◽  
Clonal Abnormalities

Abstract Numerous studies have shown that the presence, number and type of chromosomal aberrations represent an independent predictor of prognosis in B-cell chronic lymphocytic leukemia (CLL). Consequently, cytogenetic analysis is routinely performed in this disease. However, CLL lymphocytes have a poor mitotic index, generating only 40–50% of abnormal karyotypes. The rate of detection can be increased to 80% by interphase FISH analysis. Since some aberrations, i.e. those not involving the classical regions (13q, 12, 11q, 17p, and 6q), can escape FISH detection, there has been great interest in improved culturing methods with an immunostimulatory CpG oligonucleotide (CpG). We performed a multicentric cytogenetic study to assess the impact of 2 different culturing procedures on the detection of clonal abnormalities in 159 consecutive unselected cases with CLL referred to our centers for routine analysis from October 2007 to July 2008. Dual 72 hours cultures of bone marrow or peripheral blood were set up with the addition of either a conventional B cell mitogen (TPA) or CpG and interleukin-2 (IL2). Cytogenetic analysis was performed on both cultures. FISH analysis using a CLL probe panel analyzing 1–6 regions (13q, centromere 12, 11q, 17p, 6q and 14q32) was also applied on uncultured material, on CpG and/or on TPA culture in 146 cases. Quality of banding and proliferation capacity were assessed in 38 cases. The quality was good in 17 (CpG) and 8 (TPA), intermediate in 12 (CpG) and 18 (TPA), and poor in 9 (CpG) and 12 (TPA) cases. The mitotic index was slightly higher in CpG cultures: <15 mitoses/slide were seen in 12 (CpG) and 15 (TPA) cases, 15–20 mitoses/slide in 13 (CpG) and 14 (TPA) cases, and >20 mitoses/slide in 13 (CpG) and 9 (TPA) cases, respectively. Clonal abnormalities were identified in 89 cases (56%). In 56 cases, the aberrant clone was detected in both cultures. Of these, the percentage of aberrant metaphases was similar in both cultures in 13, higher in CpG culture in 32 and higher in TPA culture in 11 cases. In 29 and 4 additional cases, a clonal abnormality was detected only in CpG or TPA culture, respectively. Thus, the percentage of abnormal karyotypes with CpG and TPA was 53 and 38%, respectively (p=0,005). “Typical” aberrations, including del(13q), +12, del(11q), del(17p) and del(6q), were detected in 16, 26, 15, 9, and 7 (CpG) cases, and in 10, 20, 16, 8, and 3 (TPA) cases, respectively. Translocations (balanced and unbalanced) were observed in 46 (CpG) and 27 (TPA) cases, whereas aberrations involving 14q32 were seen in 5 (CpG) and 4 (TPA) cases, respectively. Interphase FISH detected del(13q), +12, del(11q), del(17p), del(6q) and del(14q) in 53, 1, 5, 0, 0 and 1 cases, respectively, in which cytogenetic analysis was either normal or abnormal but did not show the specific change. Conversely, FISH did not detect del(13q), +12, del(11q), del(17p), del(6q) and del(14q) in 1, 1, 4, 1, 2 and 0 cases in which the specific change was visible at karyotypic level. FISH was performed on both CpG and TPA cultures in 9 selected cases harbouring an aberration for which a specific commercial probe was available (+12, n=3; del(13q), n=4; del(11q), n=1; and del(17p), n=1) and showing different percentages of aberrant cells in both cultures. In 3 of these cases, fresh uncultured material was also analyzed. The highest percentage of abnormal nuclei was observed in TPA culture in all cases. In the 3 uncultured samples the percentage of aberrant nuclei was similar to the CpG culture. In conclusion, our results confirm an increased detection rate of abnormalities in CLL by using CpG/IL2 stimulation. Interphase FISH can further increase the detection rate of recurrent abnormalities. However, neither cytogenetics nor FISH detected all aberrations, demonstrating the complementary nature of these techniques and the necessity of performing both.

Karyotype Results From CpG Oligodeoxynucleotide Stimulated Chronic Lymphocytic Leukemia (CLL) Cultures Are Consistent Among Laboratories: a CLL Research Consortium (CRC) Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1614-1614
Author(s):  
Nyla A. Heerema ◽  
John C. Byrd ◽  
Paola Dal Cin ◽  
Marie L Dell' Aquila ◽  
Prasad Koduru ◽  
...  
Keyword(s):  
B Cell ◽  
Prospective Trial ◽  
Pokeweed Mitogen ◽  
Fish Analysis ◽  
Cytogenetic Abnormalities ◽  
Interphase Fish ◽  
Cpg Oligodeoxynucleotide ◽  
Research Consortium ◽  
Clonal Abnormalities

Abstract Abstract 1614 Poster Board I-640 Background Cytogenetic abnormalities in B-cell CLL are important prognostic indicators for predicting disease progression and treatment response. Until recently, only interphase cytogenetics has been readily applicable to clinical use in CLL due to the inability of traditional mitogens to promote effective metaphase cytogenetic identification. Recently, cytokine or CpG oligonucleotide stimulation has been utilized to promote efficient metaphase analysis. One concern with this approach is the actual clonality and reproducibility of such clones when examined by different cytogenetic laboratories. The CLL Research Consortium (CRC) conducted a prospective trial to test (1) whether CpG would enhance detection of abnormal clones and (2) whether the CRC cytogenetic laboratories would achieve similar results when testing the same patient samples. Methods Initially, one laboratory compared stimulation of CLL cells using CpG versus pokeweed mitogen (PWM) + 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in the same samples. To test the reproducibility of CpG stimulation, fresh blood samples from 1 normal control and 12 CLL patients were collected at one site and distributed (blinded to phenotype and prior cytogenetic results) to 5 CRC cytogenetic laboratories where they were cultured for 3 days using CpG stimulation, harvested, banded and analyzed utilizing standard laboratory procedures. When possible, each laboratory analyzed 20 metaphases per case. Interphase FISH analysis for CLL (including probes for chromosomes 6q, 11q, 12, 13q, 17p, and IGH/CCND1) was also done on each sample. Results In the PWM+TPA versus CpG comparison, more cases were found to have clonal abnormalities with CpG stimulation (147 of 229, 64%) than with PWM+TPA (110 of 229, 48%; P=0.0005). All clonal abnormalities detected in the PWM+TPA cultures were also observed in the CpG cultures. In the 5-laboratory CpG comparison, the results were compiled and compared to the concurrent FISH results. The CpG karyotypes were concordant with the FISH results. The control case had a normal CpG-stimulated karyotype in all 5 laboratories. Three cases exhibited a complex karyotype; one of these also exhibited 11q-, one had 17p-, and one had neither. The cytogenetic descriptions varied modestly among labs, but all identified the complex clones. Every case including the control exhibited some nonclonal abnormal cells, but no pattern was detected among the 5 labs. When an abnormal clone was found by only 1 or 2 labs, it was present in only a very small number of cells. A small 13q- clone was observed in 2 cases in 1 and 2 labs (3 of 20 and 5 of 50 cells, respectively), and was confirmed by interphase FISH. A single lab found 2 of 30 cells with a t(12;15) in one case. Conclusions Abnormal clones in CLL are more readily detected with CpG stimulation than with traditional B-cell mitogens. The clonal abnormalities revealed by CpG stimulation are consistent with the “gold standard” interphase FISH results, and are reproducible among different cytogenetic laboratories. We have no evidence that CpG oligonucleotides create new clonal B-cell populations in vitro during 3 days of cell culture. CpG stimulation in vitro reveals clonal cytogenetic abnormalities and complexity in CLL that should be evaluated as potential independent prognostic parameters. Disclosures Kay: Biogenc-Idec, Celgene, Genentech, genmab: Membership on an entity's Board of Directors or advisory committees; Genentech, Celgene, Hospira, Polyphenon Pharma, Sanofi-Aventis: Research Funding.

CpG Oligonucleotide Combined with Interleukin-2 Reveals Unexpected Chromosomal Lesions In B-CLL

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2411-2411
Author(s):  
Paolo Bernasconi ◽  
Marina Boni ◽  
Irene Dambruoso ◽  
Ilaria Giardini ◽  
Paola Maria Cavigliano ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Chromosomal Rearrangements ◽  
Interleukin 2 ◽  
Precise Definition ◽  
Leukemic Cells ◽  
Pokeweed Mitogen ◽  
Complex Karyotype ◽  
Cpg Oligonucleotide ◽  
Definition Of ◽  
Clonal Abnormalities

Abstract Abstract 2411 In B-CLL the precise definition of the chromosomal pattern has always been a very difficult goal as leukemic cells poorly respond to the traditionally used set of mitogens. Thus, conventional cytogenetic studies (CC) have always been replaced by interphase FISH (iFISH) analyses. However, recent studies have demonstrated that the CpG oligonucleotide plus interleukin-2 (ODN+IL-2) stimulation can effectively increase the detection rate of chromosomal abnormalities by inducing metaphase spreads from B-CLL leukemic cells. Based on these data, we decided to compare the results obtained by the ODN+IL2 combination, the pokeweed mitogen (PKWM) stimulation and iFISH in ninety-one B-CLL patients diagnosed at our Institution between January 2007 and July 2010. In addition, we evaluated any possible correlation with other prognostic markers and clinical parameters. There were thirty-eight females and fifty-three males with a median age of 64 years (range 42–83). According to Binet, sixty-three patients (69.2%) were considered as stage A, seventeen (18.7%) as stage B and eleven (12.1%) as stage C. PKWM did not provide any mitotic figure in thirteen patients (14.2%) and detected clonal defects in sixteen patients (17.5%). In contrast, the ODN+IL-2 combination was unable to provide metaphase spreads in three patients only (3.3%) and revealed clonal abnormalities in fifty-six patients (61.5%). In eight patients both cultures revealed an equal percentage of cells carrying the same abnormality. In addition, the ODN+IL-2 combination revealed a complex karyotype (≥ three defects) in twelve patients (13.2%), two chromosomal defects in fourteen patients (15.4%)(including five with band 17p13 rearrangement and three with band 11q13 rearrangement) and a single chromosomal defect in thirty patients (32.9%). Fifteen patients harboured various chromosomal rearrangements (16.4%). iFISH was carried out with the B-CLL FISH probe panel (Vysis, Downers Grove, IL, USA) and revealed clonal abnormalities in sixty-two patients (68.1%). The most common defects were: 13q-, +12, 11q- and 17p- having an incidence of 46.1%, 14.2%, 7.7% and 6.5%. Three patients with a normal FISH pattern presented a +12 when analysed with the ODN+IL-2 combination and five, who showed the loss of one p53 signal on iFISH, presented a structural 17p13 defect when investigated with the ODN+IL2 combination. In addition, considering the forty-two patients who harboured a 13q- on iFISH analyses, the ODN+IL2 combination revealed that in five patients this defect was included in a complex karyotype. From a clinical point of view, considering the fifteen patients with various chromosomal rearrangements nine were classified as stage A, four as stage B and two as stage C and considering the twelve patients with a complex karyotype three were considered as stage B and nine as stage C. In conclusion, the ODN+IL2 combination i) allows a precise definition of the chromosomal pattern in B-CLL patients and in our series identified clonal defects in 61% of patients; ii) reveals minor +12 clonal cell populations which may evade iFISH identification; iii) does not always identify a 13q deletion because of the sub-microscopic nature of this chromosomal defect; iv) reveals that the loss of one p53 signal on iFISH analyses is frequently due to an unbalanced rearrangement; iv) is the only technique which allows the identification of complex karyotypes and/or chromosomal translocations both associated with an advanced Binet stage. Thus, the ODN+IL2 combination should be used in conjunction with iFISH to achieve a more accurate karyotype definition in B-CLL patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Stimulation of B-cell lymphoproliferations with CpG-oligonucleotide DSP30 plus IL-2 is more effective than with TPA to detect clonal abnormalities

Leukemia ◽  
2008 ◽  
Vol 23 (3) ◽  
pp. 617-619 ◽  
Author(s):  
S Struski ◽  
C Gervais ◽  
C Helias ◽  
R Herbrecht ◽  
B Audhuy ◽  
...  
Keyword(s):  
B Cell ◽  
Cpg Oligonucleotide ◽  
Clonal Abnormalities ◽  
Stimulation Of

The T(14;20)(q32;q12) : A Rare Cytogenetic Change in Multiple Myeloma Associated with Poor Outcome

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2718-2718
Author(s):  
Marie-Christiane Vekemans ◽  
Heidi Lemmens ◽  
Chantal Doyen ◽  
Greet Bries ◽  
HIlde Demuynck ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cytogenetic Analysis ◽  
Progressive Disease ◽  
Bone Lesions ◽  
High Dose ◽  
Fish Analysis ◽  
Advanced Stage ◽  
Interphase Fish ◽  
Poor Outcome ◽  
Split Signal

Abstract Introduction: Aberrations involving immunoglobulin genes (Ig) are recurrent in Multiple Myeloma (MM) and carry prognostic significance. One of them, the t(14;20) (q32;q12) leading to overexpression of the transcription factor MAFB has been identified in myeloma cell lines, rarely in MM, and never in MGUS. The clinical significance of this cryptic aberration remains poorly unknown. The aim of the present study was to assess the frequency and prognostic value of this chromosomal change. Materials and Methods: A series of 1200 samples from patients with MM or MGUS were assessed by interphase FISH either on immunologically identified kappa/lambda positive plasmacells (I-FISH) or on CD138 purified plasmacells (PCs). Cases selected were consecutive cases sent for routine cytogenetic analysis in which a translocation involving Ig was demonstrated by FISH (split signal with the Breakapart probe, Abbott) and was shown to be distinct from t(11;14), t(4;14), t(14;16) and t(6;14) (using specific probes), respectively. A double color interphase FISH assay was applied for the detection of the t(14;20), using a set of BAC probes located on 20q11-q12: RP4-616B8 and RP3-404H4 (centromeric to MAFB, labelled in Spectrum Orange) and RP4-644L1 and RP1-94E24 (telomeric to MAFB, labelled in Spectrum Green). Results: A characteristic split signal, was observed in 10 patients (0.8%), 8 females and 2 males, aged 49–83 years (median 69). All but 2 of them suffered from MM in advanced stage (Durie and Salmon stage II in 2 and stage III in 6 patients) and displayed multiple bone lesions. The light chain isotype was kappa in 4, lambda in 3, unknown in 1. Two cases were non secreting (but showed kappa intracytoplasmic expression). The heavy chain isotype was IgG in 6, and IgA in 1. Therapy was required in all but 1 case (1 line in 1, 2 lines in 3, and 3 lines in 5 patients, respectively). The front line consisted of VAD (n=5) followed by high dose Melphalan and autologous stem cell transplantation (ASCT)(n=4), among these, 1 had a double AST and one had a reduced intensity conditioning regimen allogeneic transplantation), Melphalan-Prednisone (MP) (n=1) and MP+Thalidomide or Lenalidomide or Bortezomib (n=3). All but 1 cases treated with VAD showed response (at least PR) which persisted at least transiently after high dose therapy (2 cases relapsed after achieving response). Two patients treated upfront with MP associated with one of the new drugs responded to this regimen. The patient treated with MP alone did not respond, was subsequently refractory to Thalidomide+Dexamethasone, but responded to Bortezomib. After a median follow-up period of 10,5 months (range 1 months – 10 years), 7 patients are alive (1 with progressive disease) and 3 died because of progressive disease, 2, 19 and 120 months after diagnosis, respectively. Conventional cytogenetic analysis showed clonal aberrations in 2 cases (hypodiploid karyotypes with complex changes). FISH analysis showed a balanced t(14;20) in all cases. The second IgH allele was intact in 9 patients and was involved (subclonally) in a t(7;14)(q31;q32) in 1 patient. Associated changes were: loss of 13q in 8, and loss of 17p13 in 1 cases. In conclusion, the t(14;20)(q32;q12) is a rare change in MM, and is associated with hypodiploidy (i.e. loss of 13q), advanced stage and poor outcome.

Immunostimulatory CpG-Oligonucleotide Activated Metaphase Cytogenetics Is Feasible in Routine Diagnostics of Chronic Lymphocytic Leukaemia and Reveals More Abnormalities Than Interphase FISH.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3252-3252
Author(s):  
Claudia Schoch ◽  
Susanne Schnittger ◽  
Wolfgang Kern ◽  
Torsten Haferlach ◽  
Frank Dicker
Keyword(s):  
Chromosomal Aberrations ◽  
Interleukin 2 ◽  
Chromosome 17 ◽  
Fish Analysis ◽  
Cpg Odn ◽  
Interphase Fish ◽  
Cpg Oligonucleotides ◽  
Banding Analysis ◽  
Chromosome Banding Analysis ◽  
Trisomy 12

Abstract Genetic characterization of chronic lymphocytic leukemia (CLL) cells by fluorescence in situ hybridization (FISH) has identified genetic aberrations in 80% of CLL patients. In contrast, conventional metaphase cytogenetics detected chromosomal aberrations in only 40–50% of all cases. Immunostimulatory CpG-oligonucleotides (CpG-ODN) in combination with interleukin 2 (IL-2) have recently been reported to induce proliferation in CLL B cells. Therefore, we evaluated this stimulus for its efficacy in metaphase generation for the detection of chromosomal aberrations by cytogenetic banding techniques. In addition these results were compared with data obtained by interphase FISH. For metaphase induction 107 cells were cultured in growth medium with the CpG-ODN DSP30 and IL-2. After 2 days colchicine was added for another 24h before preparation. Of the 133 samples that were included in this study, all cases could be successfully analyzed by interphase FISH with a rate of 79% aberrations like deletions of chromosomes 13q (57%, in 38% as sole abnormality), 11q (17%), trisomy 12 (13%), 6q (7%), 17p (6%) and translocations involving 14q32 (4%). By FISH 55% of all samples showed a single aberration, 22% two aberrations and 2% 3 aberrations. In comparison, 126 cases (95%) could be successfully analyzed by cytogenetic banding techniques. 102 (81%) of the 126 samples showed chromosomal aberrations, which involved all different chromosomes. 9 cases with a normal karyotype in conventional cytogenetics revealed genetic aberrations by FISH. In all but 1 of these cases the aberrant clone represented < 30% of the cell population. In addition to the aberrations that were detected by the FISH probes, a substantial amount of other aberrations was revealed by chromosome banding analysis. Interestingly, 10 cases of a total of 27 cases without abnormalities detected by FISH displayed aberrations in chromosome analysis indicating that the true amount of CLL patients with aberrations exceeds 79%. Overall, 47 samples (37%) showed chromosomal aberrations in chromosome banding analysis in addition to FISH analysis. Compared to FISH analysis, which detected 2 cases with 3 aberrations, metaphase cytogenetics detected 22 cases with 3 or more unbalanced aberrations, which can be considered as a complex aberrant karyotype. Loss of p53 referred to as del(17p13) in FISH has attracted considerable attention, because of the poor clinical outcome of affected patients. In our study, all del(17p13) cases (n=7) displayed either a loss of the short arm of chromosome 17 (n=6) or a complete loss of chromosome 17 (n=1) indicating that chromosomal regions in addition to the p53 locus might be relevant for this phenotype. Furthermore, numerous recurrent aberrations have been identified in this study beyond the aberrations that are detected by FISH. Of note are gains of 2p and 3q, losses in 11q13 and gains in 11q23–25, gains in 13q31–34, gains of 17q21–25 and cases with trisomy 18 and 19, which occurred in parallel to trisomy 12. The results of the present study show that immunostimulatory CpG-oligonucleotides plus interleukin 2 are a simple and cheap stimulus for efficient metaphase induction in CLL. The rate of aberrations detected by conventional banding techniques was even slighty increased compared to FISH analysis, however, the complexity of cytogenetic aberrations is underestimated by FISH analysis in a large portion of CLL cases (37%).

Stimulation of B-Cell Mature Malignancies with the CpG-Oligonucleotide DSP30 and Interleukin-2 for Improved Detection of Chromosome Abnormalities.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1955-1955 ◽  
Author(s):  
Aurelia Meloni-Ehrig ◽  
Jeanne Meck ◽  
Nicole Christacos ◽  
JoAnn Kelly ◽  
Ludmila Matyakhina ◽  
...  
Keyword(s):  
B Cell ◽  
Cytogenetic Analysis ◽  
Prognostic Significance ◽  
Interleukin 2 ◽  
Chromosome Abnormalities ◽  
Dependent Manner ◽  
B Cell Lymphomas ◽  
Lymphoid Malignancies ◽  
Conventional Cytogenetics ◽  
The Impact

Abstract Abstract 1955 Poster Board I-978 The detection of chromosome abnormalities in mature B-cell neoplasms by conventional cytogenetics remains difficult, mainly due to the low proliferative rate of mature lymphoid cells. The current FISH panel for chronic lymphocytic leukemia (CLL) is designed to detect some of the more common abnormalities of prognostic significance in CLL [i.e., del(6q), del(11q), +12, del(13q), del(17p)]. This CLL FISH panel has improved the detection rate of these markers by making it possible to obtain cytogenetic information from interphase cells; however, as it is limited to only these 5 markers, it cannot detect all abnormalities associated with CLL. More importantly, the impact of other chromosome abnormalities on prognosis and disease progression, with and without the presence of these 5 prognostic markers, is not known. CpG-oligodeoxynucleotides (ODNs) such as DSP30 activate cells of the immune system in a sequence-dependent manner and promote proliferation of CLL cells in vitro [Decker et al. Blood 2000;95:999-1006]. They also upregulate costimulatory molecules and potential target antigens during immunotherapy. The use of DSP30 in combination with interleukin 2 (IL2) has proven effective in increasing the detection of chromosome abnormalities in CLL [Dicker et al. Blood 2006;108:3152-60] and other mature B-cell lymphoid malignancies by conventional cytogenetics [Struski et al. Leukemia 2009;23:617-9], when compared to the well-established B-cell mitogens. In our extensive clinical experience of incorporating DSP30/IL2 into our culture media, this cocktail has significantly increased the detection of chromosome abnormalities in CLL by conventional cytogenetics, from 55% to greater than 80%. We thus decided to investigate if various other lymphoid malignancies would respond to the mitogen activity of DSP30/IL2 as well as or better than CLL. Specifically, we evaluated 812 cases of mature B-cell lymphoid malignancies that were abnormal by flow cytometry, morphology, or cytogenetic analysis. All samples (bone marrow or blood) were cultured for approximately 72 hours using the DSP30/IL2 mitogen cocktail. Of these 812 cases, 746 (91%) provided sufficient mitotic index and quality for a complete cytogenetic analysis and interpretation. Of the CLL cases (n=509), 79 were initially interpreted as normal by conventional cytogenetic analysis, but were later interpreted as abnormal by FISH for deletion 13q only. In view of the known cryptic nature of this deletion in CLL, these cases were not included in the study, leaving a total of 430 CLL cases, and thus bringing the total number of cytogenetically successful study cases to 667. In addition to the 430 CLL cases, there were 14 variant CLLs; 36 diffuse large B-cell lymphomas (DLBCLs); 35 follicular lymphomas; 34 non-Hodgkin lymphomas (not further specified); 29 marginal zone B-cell lymphomas of splenic type (sMZBCL); 27 mantle cell lymphomas (MCLs), of which 8 were blastoid; 16 MZBCL of MALT type; 13 hairy cell leukemias (HCLs); 12 lymphoproliferative disorders (not further specified); 10 lymphoplasmacytic lymphomas (LPLs); 6 Burkitt lymphomas; 3 Hodgkin lymphomas; and 2 B-cell prolymphocytic leukemias (PLLs). Of particular interest is the fact that we detected clonal abnormalities in 100% of HCLs, blastoid MCLs, variant CLLs, and B-cell PLL, as well as in 97% of sMZBCLs, 89% of DLBCLs, and 80% of LPLs This is of great importance since HCLs and LPLs are rarely abnormal by conventional cytogenetics using the more traditional combinations of mitogens making it difficult to identify markers of prognostic significance. In conclusion, our findings demonstrate that the DSP30/IL2 cocktail induces proliferation of various B-cell mature lymphoid disorders and that its mitogenic action is not limited to CLL. We are continuing to develop our understanding of the considerable response of specific lymphoid malignancies to the DSP30/IL2 cocktail by correlating additional clinical data, and hope that the end result will open new avenues in regards to prognostic outcome and therapeutic approaches. Disclosures: No relevant conflicts of interest to declare.

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