Diffuse large B-cell lymphoma carrying both t(3 ; 7)(q27 ; p12) and t(8 ; 14)(q24 ; q32)

We report a 60-year-old man with diffuse large B-cell lymphoma harboring both t(3 ; 7)(q27 ; p12) and t(8 ; 14)(q24 ; q32). Although he received six courses of conventional combination chemotherapy plus rituximab, early relapse occurred. Four courses of an intensive salvage regimen and high-dose chemotherapy with autologous peripheral blood stem cell transplantation were performed. The patient has remained in complete remission for over 24 months. This case is noteworthy because both genetic abnormalities are implicated in lymphomagenesis.     

Establishment and characterization of acute B-cell lymphocytic leukemia cell line showing (8;14) and (14;18) chromosome translocation

Cell line KHM-2B expressing two oncogene products, c-myc and bcl-2, was established from a patient with acute lymphocytic leukemia with an 8;14 and 14;18 chromosome translocation. Surface marker studies of the cell line showed that the cells were positive for HLA-DR, CALLA (CD10), B1 (CD20) and B4 (CD19), but negative for T11 (CD2). The fresh cells from peripheral blood of the patient had no surface immunoglobulins, whereas KHM-2B cells were positive for mu.lambda type surface immunoglobulin. A cytogenetic analysis of the cell line revealed two translocations, t (8;14) (q24;q32) and t(14;18)(q32;q21). Rearrangement of the c-myc and bcl-2 genes was detected by Southern blot analysis of the KHM-2B DNA. Northern blot analysis revealed production of c-myc and bcl-2 mRNAs. These results indicated that two oncogenes were activated by two translocations to immunoglobulin genes.     

Double-hit lymphoma with t(8;14)(q24;q32) and t(12;14)(q24;q32) chromosomal translocations

A 50-year-old man presented with an ileocecal tumor and a large amount of ascites. Lymphoma cells obtained from the ascitic fluid were CD10(+), CD20(+), CD38(+), HLA-DR(+), BCL6(-), MUM1/IRF4(+), BCL2(+), and immunoglobulin μ/γ(+). The karyotype determined by G-banding and spectral karyotyping was 46, XY, der(3)t(1;3)(q12;p12), -4, +7, t(8;14)(q24;q32), t(12;14)(q24;q32), der(17)t(4;17)(q21;p11). Fluorescence in situ hybridization disclosed that 93% of interphase cells were positive for the c-MYC and immunoglobulin heavy chain gene fusion. The patient was treated with intensive chemo-immunotherapy, resulting in a complete response. The t(8;14)-t(12;14) double-hit may have generated molecular abnormalities analogous to those of a previously cloned three-way translocation t(8;12;14).     

A plasma cell leukemia patient showing bialleic 14q translocations: t(2;14) and t(11;14).

We report here an IgG/lambda-type plasma cell leukemia patient showing bialleic 14q32 translocations. All immunoglobulins were suppressed in this patient, but a small amount of monoclonal IgG was detected by immunoelectrophoresis. Two cells of six peripheral blood mononuclear cells showed 46,XY,t(2;14)(q11;q32), i(8)(q10), t(11;14)(q13;q32), del(12)(q13.1) by karyotypic analysis. We confirmed the juxtaposition of IgH and PRAD1/Cyclin D1 genes by fluorescent in situ hybridization and overexpression of the PRAD1/Cyclin D1 gene, but Southern analysis showed no bcl-1 rearrangement. We analyzed the t(2;14)(q11;q32) using DNA fragments derived from childhood B-chronic lymphocytic leukemia cases bearing t(2;14)(p13;q32). Southern and Northern analyses demonstrated no alteration of these genes, indicating that this t(2;14) was different from that of childhood B-chronic lymphocytic leukemia. At the IgH loci, Southern analysis showed two rearranged bands and one germ-line band of JH. Cmicro was deleted on one rearranged allele but remained on the other, suggesting that the chromosome translocation occurred after productive class switch recombination on the Cmicro deleted allele.     

Quantitative assessment of disease involvement by follicular lymphoma using real-time polymerase chain reaction measurement of t(14;18)-carrying cells

Chromosomal translocation t(14:18)(q32;q21) is one of the most common karyotypic abnormalities in non-Hodgkin's lymphomas. It occurs in more than 85% of follicular lymphoma (FL) cases. Real-time polymerase chain reaction (Q-Rt-PCR) analysis using double-labeled fluorogenic probes is a new tool in the detection and quantification of t(14;18)-carrying cells. We analyzed 239 specimens with Q-Rt-PCR to detect and quantify t(14;18)-carrying cells. To investigate the clinical usefulness of the quantitative assessment, we analyzed the clinical correlation with 92 FL patients of varying clinical status. Of 59 previously untreated patients, patients with stage IV disease had significantly higher quantities of t(14;18)-carrying cells measurable in the bone marrow or the peripheral blood than patients in clinical stages I to III (P = .003 and .043, respectively). Moreover, of the 33 posttherapy patients. the patients in complete remission appeared to have lower detectable levels of t(14;18)-carrying cells than patients in partial remission or with recurrent disease. Q-Rt-PCR permits a sensitive and quantitative assessment of the extent of disease involvement in patients with t(14;18)-carrying FL. The technique has the potential to be a useful tool in the diagnosis of FL, disease assessment, and prognosticating patients' clinical outcomes.     

Translocations t(X;14)(q28;q11) and t(Y;14)(q12;q11) in T-cell prolymphocytic leukemia

We report a case of T-cell prolymphocytic leukemia (T-PLL) in a 41-year-old male. Classical cytogenetic, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies of a blood sample obtained at diagnosis revealed the co-existence of t(X;14)(q28;q11), t(Y;14)(q12;q11) and a ring chromosome derived from i(8)(q10). Immunophenotypic studies revealed involvement of T-cell lineage, with proliferation of CD4(-) CD8+. The co-existence of two translocations involving both sex chromosomes in a case of T-PLL is rare. Chromosomal instability associated with the disease progression may have allowed the emergence of cell clones with translocations involving the sex chromosomes and the ring chromosome observed.     

Distribution of t(14;18)-positive, putative lymphoma precursor cells among B-cell subsets in healthy individuals

The t(14;18)(q32;q21) is the characteristic chromosomal translocation of follicular lymphoma (FL). Highly sensitive polymerase chain reaction (PCR) techniques can also detect t(14;18)-sequences in the blood and lymphoid tissues of healthy individuals (HI). The aim of this study was to determine the immunophenotypic markers of t(14;18)-positive cells in HI and to relate these features to lymphocyte maturation. B cells from 10 subjects with t(14;18)-positive and three subjects with t(14;18)-negative peripheral blood mononuclear cells (PBMC) were fluorescence-activated cell sorted for antigen-naïve (CD27⁻), immunoglobulin M (IgM) memory (IgM⁺CD27⁺) and switched memory (IgM⁻ CD27⁺) cells. t(14;18)-recombinations were detected by quantitative PCR. Among PBMC-positive subjects, t(14;18)-frequency was significantly higher in IgM memory (median: 380/10⁶) than in antigen-naïve (median: 16/10⁶) or switched memory (median: 5/10⁶) B cells. All PBMC-negative subjects nevertheless had detectable t(14;18) in sorted B cells; levels were lower than in PBMC-positive subjects, but had the same relative predominance. These results suggest that t(14;18) is generated during early B-cell development in the bone marrow and that affected cells may mature and expand in germinal centres. t(14;18)-frequency was highest in IgM memory cells, a B-cell subset that shares immunophenotypic similarities with FL. The significance of these cells as lymphoma precursors or indicators of lymphoma risk remains to be established.     

Case of acute lymphoblastic leukemia presenting with t(14;18)/BCL2, t(8;14)/cMYC, and t(1;2)/FCGR2B

The majority of follicular lymphoma and Burkitt's lymphoma are associated with reciprocal translocations involving BCL2 and cMYC, respectively. Unusual reports of aggressive lymphoma presenting with both translocations have been described as well as rare cases with a third structural alteration usually involving BCL6. The patient described here presented with aggressive high-grade lymphocytic leukemia, FAB subtype L2 (ALL-L2), and three reciprocal translocations, t(14;18)(q32;q21), t(8;14)(q24.1;q32), and t(1;2) (q22-23;p13). Despite immature morphology the leukemic blasts had a mature B-cell phenotype; they were positive for surface immunoglobulin heavy chains and negative for CD34, TdT, and CD10. Most reported dual t(14;18)/t(8;14) cases have not shown sIg and were positive for CD10. Molecular genetic analyses showed the typical rearrangements of BCL2 and cMYC as well as the FCGR2B gene on chromosome 1q23. The occurrence of a third oncogene rearrangement in association with the dual BCL2, cMYC translocations in ALL patients is very rare. To our knowledge, this is the first case where the third hit involves the FCGR2B locus. This report reiterates the poor prognosis associated with activation of cMYC together with elevated Bcl-2 expression. These data also support recent evidence that dysregulation of FCGR2B may play a role in tumor progression.     

Case of B-Cell Lymphoma with Rearrangement of the <Emphasis Type="Italic">BCL1, BCL2, BCL6</Emphasis>, and <Emphasis Type="Italic">c-MYC</Emphasis> Genes

We managed a peculiar case of lymphoma showing immunohistochemical overexpression of cyclin D1. At initial examination the patient had meningeal lymphomatosis and general lymphadenopathy. Histologic examination of biopsy specimens of inguinal lymph nodes showed tumor cells and vague nodular growth resembling lymphoblasts. The results of flow cytometric analysis were positive for CD10, CD20, CD103, and immunoglobulin G (IgG) and Ig kappa and were negative for CD5, CD23, and terminal deoxynucleotidyl transferase activity. Results of immunohistochemical analysis of paraffin-embedded specimens were positive for cyclin D1 and Bcl2 in the tumor cells. Sixty percent of tumor cells had positive results for MIB1/Ki67. Cytogenetic and molecular studies revealed tumor cells simultaneously had t(14;18)(q32;q21), t(11;22)(q13;q11), t(8;14)(q24;q32), and t(3;14)(q27;q32) with the rearrangement of BCL1, BCL2, BCL6, and c-MYC genes. Lymphadenopathy showed a quick and complete response to doxorubicin-containing systemic chemotherapy with rituximab, but the central nervous system disease progressed and killed the patient.     

A new human B-cell non-Hodgkin's lymphoma cell line (Karpas 422) exhibiting both t (14;18) and t(4;11) chromosomal translocations

A unique B-cell non-Hodgkin's lymphoma (NHL) cell line (Karpas 422), bearing both t(14;18) and t(4;11) chromosomal translocations as well as several other chromosomal abnormalities, has been established from the pleural effusion of a patient with chemotherapy-resistant NHL. This cell line has the same karyotypic features as malignant cells from the patient. The major cell clone is characterized chromosomally by 46,XX t(2;10)(p23;q22.1), t(4;11)(q21.3; q23.1), t(14;18)(q32.1;q21.3), t(4;16)(q21.3;p13.1). Both phenotypically and genotypically, the cell line has features of a mature B-cell neoplasm with no evidence for commitment to other lineages. Rearrangements of the C-ETS-1 oncogene and N-CAM-1 and CD3 genes that map to 11q23 were not detected by conventional Southern analysis. BCL-2 was rearranged within the major breakpoint cluster. The K422 cell line has a unique karyotype; this is the first occasion that the t(4;11) translocation has been described in a t(14;18) lymphoma. The cell line will be of value in determining the molecular nature of the t(4;11) translocation.     

Acquisition of t(11;14) in a patient with chronic lymphocytic leukemia carrying both t(14;19)(q32;q13.1) and +12

A rare recurrent chromosomal translocation, t(14;19)(q32;q13), has been identified in a variety of B‐cell malignancies, including chronic lymphocytic leukemia (CLL). We report a unique case of CLL in a patient carrying both trisomy 12 and t(14;19) (q32;q13.1), in whom t(11;14)(q13;q32) developed at relapse. The patient was a 77‐yr‐old woman, and her lymphoma cells at presentation showed CD5⁺, CD10^?, CD19⁺, CD20⁺(dim), CD23⁺, CD38⁺, and CD11c⁺. At relapse, the patient's lymphoma cells showed positive staining for cyclin D1 in addition to CD5, CD20, and CD23. Lymphoma cells in specimens at both presentation and relapse were positive for lymphoid enhancer factor 1 (LEF1) and negative for sex‐determining region Y‐box 11 (SOX11). IGH‐BCL1 FISH became positive at relapse. Split FISH assay using BCL1, BCL3, IGH, and CCND1 probes on lymph node specimens obtained at presentation and at autopsy confirmed that the translocation of BCL3 was solely detected in the lymph node at presentation and detected BCL3 and CCND1 translocations in the specimen at autopsy. These observations indicated that IGH‐BCL3 and IGH‐CCND1 had occurred in the same clone after treatment of the disease. In line with immunohistochemical and cytogenetic studies, additional PCR analysis of the FR3‐JH region showed the same sequence derived from IGHV4‐34 in specimens obtained at disease onset and relapse.     

Large variation in t(11;14)(q13;q32) and t(14;18)(q32;q21) translocation product size is confirmed by sequence analysis of PCR products

Polymerase chain reaction is commonly used to detect t(11;14)(q13;q32) and t(14;18)(q32;q21) chromosomal translocations associated with mantle cell lymphoma and follicular lymphoma. We tested a total of 482 samples from patients with suspected non-Hodgkin's lymphoma and sequenced unusual-sized t(11;14)(q13;q32) and t(14;18)(q32;q21) products from 33 of these patients. BCL-1 or BCL-2 gene rearrangements were confirmed in 23 of 33 patients (70%). Considerable size variation was observed using t(11;14) primers, with MTCA and MTCB t(11;14) products ranging from 234 to 934 bp and 143 to 560 bp respectively. Less variability was observed for t(14;18) Major Breakpoint Region (MBR) products (100-252 bp) but Minor Cluster Region (MCR) products ranged from 217 to 498 bp. We demonstrate the utility of sequence analysis to confirm unusual-sized translocation products and reduce false-positive results because of nonspecific amplification.     

Thermostable DNA polymerase chain amplification of t(14;18) chromosome breakpoints and detection of minimal residual disease.

Achieving the capacity to detect minimal numbers of neoplastic cells is a major cancer diagnostic challenge. Chromosomal translocations such as the t(14;18)(q32;q21) found in follicular and some nonfollicular lymphomas provide a tumor-specific molecular marker. The 14;18 breakpoints are focused at one of six immunoglobulin heavy chain joining (JH) regions on chromosome 14 and a small major breakpoint region (MBR) of the BCL2 gene on chromosome 18. We utilized universal oligonucleotide primers of a region 5' to the BCL2 MBR and at the 3' end of JH segments to initiate a DNA polymerase chain reaction that amplified these BCL2-JH junctures. Use of thermostable DNA polymerase enabled annealing and synthesis steps at temperatures approaching the melting point of the primers, providing a sensitive and specific assay capable of detecting 1 lymphoma cell in 10(6) normal cells. This technique identified the subclinical presence of leukemic cells in all seven patients examined, including two in clinical remission. It also assessed the effectiveness of protocols designed to purge malignant cells from marrow. Moreover, this approach enabled the rapid DNA sequencing of chromosomal breakpoints without their molecular cloning. This assay markedly refines the capacity to detect minimal residual disease and should improve the ability to determine the stage of disease, stratify treatment, and evaluate therapy.     

t(14;18)(q32;q21)-bearing pleural MALT lymphoma with IgM paraproteinemia: value of detection of specific cytogenetic abnormalities in the differential diagnosis of MALT lymphoma and lymphoplasmacytic lymphoma

A 67-year-old woman presented with a pleural effusion and a tumor in the right pleural wall. Histological examination of thoracoscopic tumor and pleural biopsy specimens showed infiltration by medium sized cells, some of which showed plasmacytoid differentiation. In view of the presence of IgM paraproteinemia and bone marrow involvement by lymphoma cells, the patient was diagnosed tentatively as having lymphoplasmacytic lymphoma (LPL). However, chromosomal analysis of the cells in the pleural fluid detected t(14;18)(q32;q21), while fluorescence in situ hybridization was positive for 11% of the MALT1 split signal. Because of the presence of characteristic genetic abnormalities and notable extranodal involvement, the patient was diagnosed as having MALT lymphoma. She was treated with three courses of cladribine and rituximab, and achieved complete regression of the tumor. In this case the detection of t(14;18)(q32;q21) involving IGH and MALT1 was useful for the differential diagnosis of LPL and MALT lymphoma.     

Lack of correlation between numbers of circulating t(14;18)-positive cells and response to first-line treatment in follicular lymphoma

In follicular lymphoma, the t(14;18) status of the peripheral blood and bone marrow analyzed by polymerase chain reaction (PCR) is assumed to correlate with disease activity in patients with relapsed disease. The clinical significance of quantitating circulating lymphoma cells by real-time PCR is reported in patients on first-line treatment. Thirty-four consecutive patients with previously untreated follicular lymphoma and detectable t(14;18)-positive cells in pretreatment peripheral blood samples were monitored. All patients were treated with standard chemotherapy in combination with interferon alfa-2b. Before and after induction therapy, blood samples were taken for quantitative analysis of t(14;18). At presentation, a median of 262 t(14;18)-positive cells per 75,000 normal cells was found (range, 1-75 000). Patients with lower numbers of circulating tumor cells more frequently had bulky disease (P =.02). Seventy-nine percent of the patients responded clinically to treatment. In 22 of 28 patients, including 4 patients in whom treatment had failed clinically, the number of circulating t(14;18)-positive cells decreased to undetectable or low levels after therapy. In the remaining responding patients, circulating tumor cells persisted after therapy. These quantitative data on circulating t(14;18)-positive cells call into question the usefulness of molecular monitoring of the blood in a group of patients with follicular lymphoma uniformly treated with a noncurative first-line regimen. T(14;18)-positive cells decreased in peripheral blood after treatment, irrespective of the clinical response. Therefore, the significance of so-called molecular remission should be reconsidered in follicular lymphoma. (Blood. 2001;98:940-944)     

Lymphoma-associated translocation t(14;18) in blood B cells of normal individuals

Successive oncogenic steps are necessary to generate cancer. In many B- cell lymphomas, chromosomal translocations are considered to be an early oncogenic hit. We investigated whether the lymphoma-associated t(14;18) involving the BCL2 oncogene can occur outside the context of malignancy. To this end, we extensively screened blood cells from healthy blood donors by a very sensitive seminested polymerase chain reaction (PCR) for breakpoint junctions at JH1-5 on 14q32 and the major breakpoint region of BCL2 on 18q21. In each individual, mononuclear cells, granulocytes, flow-sorted B cells, and T cells were separately tested in five to seven independently performed PCRs (in total, 0.5 x 10(6) to 1.0 x 10(6) cells per fraction per individual). Amplification products that hybridized with an internal BCL2 probe and a JH probe were sequenced. Six of nine individuals harbored t(14;18) breakpoints. Translocations were restricted to B cells, with an estimated frequency of 1 in 10(5) or less circulating B cells. In total, 23 of 51 experiments on B cells were positive in contrast to 1 of 48 on T cells and 2 of 47 experiments on granulocytes. Consistent with the presence of 4.7% to 13.0% B cells in the mononuclear cell fractions, only very few (4 of 47) tests were positive in these fractions. Sequence analysis showed that four of six individuals harbored two to five unrelated t(14;18)-carrying B-cell clones. All breakpoints had a structure similar to that in follicular lymphoma. We propose that B cells with the t(14;18) translocation are regularly generated in normal individuals, but that only very few cells with the translocation will acquire the additional oncogenic hits necessary to establish the malignant phenotype.     

Significance of extra 18q- chromosome in Japanese t(14;18)-positive lymphoma

Karyotype evolution of t(14;18)-positive lymphoma was studied in 13 Japanese patients. The extra 18q- chromosome, found in six of ten patients with complex karyotypes, was the most common change subsequent to a t(14;18)(q32;q21) chromosome translocation. The additional change was interpreted as being a duplication of an 18q- derived from a t(14;18). The six patients had transformed histology of follicular small cleaved cell lymphoma or diffuse large cell lymphoma, and five of them had extranodal expansion associated with a poor prognosis. These findings indicate that the extra 18q-, together with other chromosome abnormalities, is closely associated with the advanced grade disease of t(14;18)-positive lymphoma, and the extra chromosome is evolutionally comparable with the second Philadelphia (Ph1) chromosome often found in the blastic phase of chronic myelocytic leukemia carrying a t(9;22)(q34;q11). In addition, since the extra 18q- is rarely found in American patients with t(14;18)-positive lymphoma, there appears to be a difference in the karyotype evolution between Japanese and American patients.     

Immune pancytopenia associated with a leukemic B-cell tumor carrying t(14;18)(q32;q21) translocation

We report a 75-year-old man who was initially suggested to have acute leukemia. The hemoglobin level was 3.8 g/dL, white cell count was 7,700/μL with an absence of mature neutrophils and 69.0% leukemic cells, and platelet was 0.4 × 10(4)/μL. Coombs' antiglobulin test was positive. Leukemic cells were CD5(-), CD10(+), CD20(+), CD23(-), and IgG/λ(dim+). The bone marrow consisted of normal hematopoietic precursors, whereas fluorescence in situ hybridization detected the BCL2/IgH fusion gene. He was treated with rituximab-containing chemotherapy, resulting in the resolution of pancytopenia. The underlying disease was a leukemic B-cell tumor with t(14;18)(q32;q21), and the pancytopenia was mainly caused by autoimmune mechanisms.     

Dynamics of circulating t(14;18)-positive cells during first-line and subsequent lines of treatment in follicular lymphoma

In follicular lymphoma the t(14;18) might be useful as a tumor marker in predicting the quality of the response to treatment. We investigated whether analyzing numbers of t(14;18)-positive cells in peripheral blood correlated with remission status in individual patients receiving a variety of treatments. Numbers of circulating t(14;18)-positive cells were determined by real-time polymerase chain reaction (PCR) technique. Disease parameters and response to treatment were related to the pre- and post-treatment numbers of circulating t(14;18)-positive cells for 53 follicular lymphoma patients. In these 53 patients, 70 treatment episodes were investigated. A content of more than 328 t(14;18)-positive cells per 75,000 cells prior to therapy correlated with the more advanced stage IV disease (P=0.01), bone marrow involvement (P<0.01), and overt leukemic lymphoma (P=0.04). Therapy episodes that cleared circulation from t(14;18)-positive cells with more than one log resulted in a significantly longer progression-free survival than treatment episodes with less than one log decline (26 versus 12 months, respectively) (P<0.01). After first-line treatment episodes, numbers of circulating t(14;18)-positive cells declined in fairly all cases, irrespective of the clinical response. However, for second or later lines of treatment, declining numbers of lymphoma cells correlated with a clinical remission, whereas increasing numbers of lymphoma cells were associated with clinically stable or progressive disease. From this, we conclude that quantitation of circulating t(14;18)-positive cells in peripheral blood is of only limited clinical significance in predicting treatment efficacy for the individual follicular lymphoma patient.Supported by an unrestrictive grant from Schering-Plough (JMMR)     

Follicular lymphoma with t(8;14)(q24;q32): a distinct clinical and molecular subset of t(8;14)-bearing lymphomas.

The presence of the translocation t(8;14)(q24;q32) has not been well described in follicular lymphoma (FL). In a consecutive series of 278 karyotypically abnormal non-Hodgkin's lymphomas (NHL), six patients with FL showing a t(8;14) without a t(14;18)(q32;q21) were identified. They ranged in age from 45 to 73 years. The cell type was mixed in four patients, small-cleaved in one, and large-cleaved in one; four cases also contained diffuse areas. All cases tested displayed monoclonal surface Ig. The clinical courses were consistent with the histologic subtypes, being less aggressive than other t(8;14)-bearing NHL. In five cases, frozen tissue was available for Southern blotting. The BCL2 gene showed a germline configuration when studied with the MBR, MCR, and 5' cDNA probes. The MYC gene also appeared unrearranged using an exon-1 probe with EcoRI or HindIII digestion. Analysis of the Ig heavy chain (IgH) gene with a JH region probe and BamHI or EcoRI digestion showed only one rearranged band in all cases, indicating that the 14q32 breakpoint did not lie in either the J or switch-mu (SM) regions. In four cases, the exon-1/intron-1 border of the MYC gene, a target area for point mutations in cases of t(8;14) that do not display rearrangements of the MYC gene, was enzymatically amplified and sequenced; no point mutations were identified. The indolent behavior of our six cases, and the finding that the molecular structure of the t(8;14) in these cases does not follow the pattern of breakpoint sites and point mutations defined in other histologic subtypes of NHL with this translocation, suggest that the t(8;14) in these cases is cytogenetically and molecularly distinct from the t(8;14) seen in high-grade NHLs, and is relatively ineffectual in terms of MYC deregulation, or that other genetic elements at these chromosomal sites may be involved. Further analysis of these tumors may provide insights into MYC deregulation and BCL2-independent FL.