A comprehensive flow-cytometry-based immunophenotypic characterization of Burkitt-like lymphoma with 11q aberration.

We previously described a subset of MYC translocation-negative aggressive B-cell lymphomas resembling Burkitt lymphoma, characterized by proximal gains and distal losses in chromosome 11. In the 2016 WHO classification, these MYC-negative lymphomas were recognized as a new provisional entity, 'Burkitt-like lymphoma with 11q aberration'. Here we present an immunophenotype analysis of Burkitt-like lymphomas with 11q aberration. Cells were acquired by fine needle aspiration biopsy from 10 young adult patients, 80% of whom presented recurrence-free 5-year survival. Twenty-three MYC-positive Burkitt lymphomas, including three carrying both MYC rearrangement and 11q aberration, served as controls. By immunohistochemistry, all Burkitt-like lymphomas with 11q aberration were CD20+/CD10+/BCL6+/BCL2-/MUM1-/MYC+/EBV-, usually LMO2+/CD44-/CD43- and sometimes CD56+, and showed high proliferation rate. By flow cytometry, Burkitt-like lymphoma with 11q aberration immunophenotypically resembled MYC-positive Burkitt lymphoma, except for significantly (adjusted P<0.001) more frequent CD38higher expression in Burkitt lymphoma (91% MYC-positive Burkitt lymphoma vs 10% Burkitt-like lymphoma with 11q aberration), more frequently diminished CD45 expression in Burkitt lymphoma (74% vs 10%), an exclusive CD16/CD56 and highly restricted CD8 expression in Burkitt-like lymphoma with 11q aberration (60% vs 0% and 40% vs 4%, respectively). We showed high diagnostic accuracy and effectiveness of flow cytometry in Burkitt lymphoma. CD16/CD56 expression without CD38higher and the lack of CD16/CD56 with CD38higher expression proves to be a reliable, fast, and cost-effective method for diagnosing 11q aberration and MYC rearrangements in CD10(+) aggressive lymphomas, respectively. In addition, we confirmed a pattern of an inverted duplication with telomeric loss of 11q, as a recurrent 11q abnormality, but one case presented alternative changes, possibly resulting in an equivalent molecular effect. Our findings reveal similarities along with subtle but essential differences in the immunophenotype of Burkitt-like lymphoma with 11q aberration and MYC-positive Burkitt lymphoma, important for the differential diagnosis, but also for understanding the pathogenesis of Burkitt-like lymphoma with 11q aberration.

Prognosis of patients with BRCA1-associated ovarian carcinomas depends on TP53 accumulation status in tumor cells.

OBJECTIVE: TP53 mutation is the most frequent molecular event in BRCA1-associated ovarian carcinomas. TP53 status may be a confounding factor in the evaluation of clinical importance of other proteins. We aimed to evaluate the clinical significance of BRCA1 mutations with respect to the TP53 accumulation status in 159 high-grade ovarian carcinomas. METHODS: Statistical analyses were done with the Kaplan-Meier method, log-rank test, the Cox's and logistic regression models for all patients, and in subgroups with and without TP53 accumulation (TP53+ and TP53-, respectively). RESULTS: Forty of 159 ovarian carcinomas (25.2%) were diagnosed in patients with BRCA1 germline mutations; 102 tumors (64.2%) were TP53+ and 57 (37.8%) were TP53-. Among patients with TP53+ carcinomas, BRCA1 carriers had increased odds of recurrence compared with sporadic cases (HR 2.25, P=0.003; median disease-free survival time 7.7 vs. 18.4months, respectively). In the smaller TP53- subgroup, BRCA1 mutation reduced the risk of death by 46% (HR 0.54, P=0.099, median overall survival time 42.7 vs. 28.1months), but beyond the border of significance. When the TP53 status was not taken into account, BRCA1 mutations did not show any significance, however, there was a trend toward increased odds of complete remission for women with BRCA1 mutations compared to non-carriers (OR 2.47, P=0.064). Taxane-platinum therapy showed advantage over the platinum-cyclophosphamide one in the entire group of patients and in the TP53+ subgroup. CONCLUSIONS: Our results suggest that the TP53 accumulation status determines the prognosis of BRCA1 mutation carriers with high-grade ovarian carcinomas.

BCRP mRNA and FLT3-ITD are independent poor risk factors in adult patients with acute myeloid leukemia and intermediate or normal karyotype.

PURPOSE: FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) is aberration associated with poor prognosis in AML. We have analyzed the expression of MDR-1, MRP-1, and BCRP mRNA in relation to FLT3-ITD in 100 AML adult patients with normal and intermediate karyotype. METHODS: The RQ-PCR method was performed to assess the expression of MDR-1, MRP-1, and BCRP mRNA, and the results were presented as coefficients calculated using an intermediate method according to Pfaffl's rule. RESULTS: According to univariate analysis, the following pretreatment variables negatively influenced disease-free survival (DFS): WBC count ≥25×109 /L (P=.037), MRP-1 mRNA ≥1.6818 (P=.028), BCRP mRNA ≥1.1892 (P=.004), FLT3-ITD (P=.005) and overall survival (OS): WBC count ≥25×109 /L (P=.031), MRP-1 mRNA ≥1.6818 (P=.01), BCRP mRNA ≥1.1892 (P=.01), FLT3-ITD (P=.001). When all prognostic variables were pooled into a multivariate model, we found that WBC count ≥25×109 /L (P=.026) and BCRP mRNA ≥1.1892 (P=.011). We observed trend in negative influence of FLT3-ITD on DFS (P=.057). BCRP mRNA ≥1.1892 (P=.035) and FLT3-ITD (P=.006) negatively, independently influenced the OS. CONCLUSIONS: The high expressions of BCRP mRNA calculated with Pfaffl's rule and FLT3-ITD are independent poor risk factors in adult patients with AML and intermediate or normal karyotype.

Genomic alterations of the JAK2 and PDL loci occur in a broad spectrum of lymphoid malignancies.

The recurrent 9p24.1 aberrations in lymphoid malignancies potentially involving four cancer-related and druggable genes (JAK2, CD274/PDL1, PDCD1LG2/PDL2, and KDM4C/JMJD2Cl) are incompletely characterized. To gain more insight into the anatomy of these abnormalities, at first we studied 9p24.1 alterations in 18 leukemia/lymphoma cases using cytogenetic and molecular techniques. The aberrations comprised structural (nine cases) and numerical (nine cases) alterations. The former lesions were heterogeneous but shared a common breakpoint region of 200 kb downstream of JAK2. The rearrangements predominantly targeted the PDL locus. We have identified five potential partner genes of PDL1/2: PHACTR4 (1p34), N4BP2 (4p14), EEF1A1 (6q13), JAK2 (9p24.1), and IGL (22q11). Interestingly, the cryptic JAK2-PDL1 rearrangement was generated by a microdeletion spanning the 3'JAK2-5'PDL1 region. JAK2 was additionally involved in a cytogenetically cryptic IGH-mediated t(9;14)(p24.1;q32) found in two patients. This rare but likely underestimated rearrangement highlights the essential role of JAK2 in B-cell neoplasms. Cases with amplification of 9p24.1 were diagnosed as primary mediastinal B-cell lymphoma (five cases) and T-cell lymphoma (four cases). The smallest amplified 9p24.1 region was restricted to the JAK2-PDL1/2-RANBP6 interval. In the next step, we screened 200 cases of classical Hodgkin lymphoma by interphase FISH and identified PDL1/2 rearrangement (CIITA- and IGH-negative) in four cases (2%), what is a novel finding. Forty (25%) cases revealed high level amplification of 9p24.1, including four cases with a selective amplification of PDL1/2. Altogether, the majority of 9p24.1 rearrangements occurring in lymphoid malignancies seem to target the programmed death-1 ligands, what potentiates the therapeutic activity of PD-1 blockade in these tumors. © 2016 Wiley Periodicals, Inc.

A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma.

The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.

miR expression in MYC-negative DLBCL/BL with partial trisomy 11 is similar to classical Burkitt lymphoma and different from diffuse large B-cell lymphoma.

Fast and reliable differential diagnosis of Burkitt lymphoma (BL) vs. diffuse large B cell lymphoma (DLBCL) is of major importance for therapeutic decisions and patient outcome. Aggressive B cell non-Hodgkin lymphomas (B-NHLs) that do not belong to the abovementioned entities were categorized by the current WHO lymphoma classification as "B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and BL" (DLBCL/BL). We have recently described a DLBCL/BL subgroup with recurrent chromosome 11q aberrations, resembling BL (B-NHLs[11q]). Here, we analyzed 102 prospectively collected fine needle aspirates from patients with aggressive B-NHLs in order to investigate the potential of microRNA (miR)-155, its precursor BIC, as well as miR-21 and miR-26a to differentiate BL from DLBCL, and from DLBCL/BL that include B-NHLs[11q]. Both BL and DLBCL/BL cases, including B-NHLs[11q], demonstrated significantly lower expression levels of miR-155/BIC, miR-21, and miR-26a compared to primary DLBCL. In conclusion, the miRs expression in B-NHLs[11q] provides a new suggestion, in addition to pathomorphological and clinical similarities between classical, i.e., MYC translocation-positive BL, and B-NHLs[11q], to recognize the B-NHLs[11q] subgroup of DLBCL/BL category as a MYC translocation-negative variant of BL in most cases, and points to the potential utility of miR-155/BIC/miR-21/miR-26a for the differential diagnosis of a heterogeneous category of DLBCL/BL.

Cytogenomic features of Richter transformation.

BACKGROUND: Richter transformation (RT) is the development of aggressive lymphoma in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). This rare disease is characterised by dismal prognosis. In recent years, there has been a deeper understanding of RT molecular pathogenesis, and disruptions of apoptosis (TP53) and proliferation (CDKN2A, MYC, NOTCH1) has been described as typical aberrations in RT. RESULTS: A single-institution cohort of 33 RT patients were investigated by karyotyping, fluorescence in situ hybridization and single nucleotide polymorphism/copy number (CN) arrays. Most of RTs were typically manifested by diffuse large B-cell lymphoma, not otherwise specified, among the remaining cases one was classified as high-grade B-cell lymphoma with 11q aberrations. The most frequent alterations (40-60% of cases) were represented by MYC rearrangement/gain, deletions of TP53 and CDKN2A, IGH rearrangement and 13q14 deletion. Several other frequent lesions included losses of 14q24.1-q32.33, 7q31.33-q36.3, and gain of 5q35.2. Analysis of 13 CLL/SLL-RT pairs showed that RT arised from the CLL/SLL by acquiring of 10 ~ 12 cytogenetic or CN lesions/case, but without acquisition of loss of heterozygosity regions. Our result affirmed the higher genetic complexity in RT than CLL/SLL and confirmed the linear features of RT clonal evolution as predominant. CONCLUSIONS: Cytogenomic profile was concordant with the literature data, however the role of IGH rearrangement, 14q deletion and 5q35.2 gain need to be explored. We anticipate that further characterization of RT lesions will probably facilitate better understanding of the RT clonal evolution.

Predictive role of NKCD56bright cells in monitoring the progression of chronic lymphocytic leukemia during treatment.

INTRODUCTION: Standard treatment for chronic lymphocytic leukemia (CLL) has experienced a dramatic change over the last few years. Until recently, CLL was treated using chemoimmunotherapy (CIT) with anti-CD20 monoclonal antibodies. Even though novel agents such as BTKi (Bruton Tyrosine Kinase inhibitor) and BCL2 inhibitors are the standard of care in most therapeutic settings, CIT still has its place in CLL treatment. Interestingly, little is known about its effects on the immune system of patients with CLL. Contrary to the reduction of the number of CLL cells during CIT administration, little attention has been paid to the cellular microenvironment, the evaluation of which during treatment may provide additional information about the course of the disease and prognosis and therefore was set as the aim of this study. MATERIAL AND METHODS: Flow cytometry was used to evaluate the phenotypes of different populations and subpopulations of lymphocytes in the peripheral blood (PB) of 20 patients with CLL before, during, and after CIT. RESULTS: During the CIT with R-FC (Rituximab, Fludarabine, and Cyclophosphamide) and R-B (Rituximab, Bendamustine) regimens, the sizes of the assessed populations and subpopulations of lymphocytes were dramatically reduced. Twenty-eight days after the first course of treatment, the exponential decrease of CLL cells was observed, and their number had declined to the median level of 10% of the numbers observed before the treatment. T cells, NK cells, NKCD56dim, NKT-like, and NKT-like CD56dim also decreased exponentially. After the second treatment course, a decline in the numbers of T, NK, NKCD56dim, NKT-like, and NKT-like CD56dim cells was observed, which were stable until the sixth treatment course. However, the number of NKT-like CD56bright cells decreased to the third course of treatment and then increased. The number of CLL cells in peripheral blood correlated with the number of NKCD56bright cells, influencing the treatment response. CONCLUSIONS: Upon CIT, the reduction of CLL cells is accompanied by shifts in immune cell populations, T, NK, and NKT-like cells. Monitoring changes of those cell populations in the peripheral blood may serve as an important predictive and prognostic indicator.

WT1 Gene Mutations, rs16754 Variant, and WT1 Overexpression as Prognostic Factors in Acute Myeloid Leukemia Patients.

(1) Background: The aim of our study was the complex assessment of WT1 variants and their expression in relation to chromosomal changes and molecular prognostic markers in acute myeloid leukemia (AML). It is the first multidimensional study in Polish AML patients; (2) Methods: Bone marrow aspirates of 90 AML patients were used for cell cultures (banding techniques and fluorescence in situ hybridization), and to isolate DNA (WT1 genotyping, array comparative genomic hybridization), and RNA (WT1 expression). Peripheral blood samples from 100 healthy blood donors were used to analyze WT1 rs16754; (3) Results: Allele frequency and distribution of WT1 variant rs16754 (A;G) did not differ significantly among AML patients and controls. Higher expression of WT1 gene was observed in AA genotype (of rs16754) in comparison with GA or GG genotypes­10,556.7 vs. 25,836.5 copies (p = 0.01), respectively. WT1 mutations were more frequent in AML patients under 65 years of age (p < 0.0001) and affected relapse-free survival (RFS). The presence of NPM1 or CEBPA mutations decreased the risk of WT1 mutation presence, odds ratio (OR) = 0.11, 95% CI 0.02−0.46, p = 0.002 or OR = 0.05, 95% CI 0.006−0.46, p = 0.002, respectively. We observed significantly higher WT1 expression in AML CD34+ vs. CD34−, −20,985 vs. 8304 (p = 0.039), respectively. The difference in WT1 expression between patients with normal and abnormal karyotype was statistically insignificant; (4) Conclusions: WT1 gene expression and its rs16754 variant at diagnosis did not affect AML outcome. WT1 mutation may affect RFS in AML.

PROM1, CXCL8, RUNX1, NAV1 and TP73 genes as independent markers predictive of prognosis or response to treatment in two cohorts of high-grade serous ovarian cancer patients.

Considering the vast biological diversity and high mortality rate in high-grade ovarian cancers, identification of novel biomarkers, enabling precise diagnosis and effective, less aggravating treatment, is of paramount importance. Based on scientific literature data, we selected 80 cancer-related genes and evaluated their mRNA expression in 70 high-grade serous ovarian cancer (HGSOC) samples by Real-Time qPCR. The results were validated in an independent Northern American cohort of 85 HGSOC patients with publicly available NGS RNA-seq data. Detailed statistical analyses of our cohort with multivariate Cox and logistic regression models considering clinico-pathological data and different TP53 mutation statuses, revealed an altered expression of 49 genes to affect the prognosis and/or treatment response. Next, these genes were investigated in the validation cohort, to confirm the clinical significance of their expression alterations, and to identify genetic variants with an expected high or moderate impact on their products. The expression changes of five genes, PROM1, CXCL8, RUNX1, NAV1, TP73, were found to predict prognosis or response to treatment in both cohorts, depending on the TP53 mutation status. In addition, we revealed novel and confirmed known SNPs in these genes, and showed that SNPs in the PROM1 gene correlated with its elevated expression.

Cryptic MYC insertions in Burkitt lymphoma: New data and a review of the literature.

The occurrence of MYC-negative Burkitt lymphoma (BL) has been discussed for many years. The real frequency of the MYC insertion in MYC-negative BL is still unknown. Fine-needle aspiration biopsies of 108 consecutive patients with clinicopathologically suspected BL (suspBL) were evaluated by flow cytometry, classical cytogenetics, and fluorescence in situ hybridization (FISH). We found 12 cases (11%) without the MYC rearrangement by FISH with a MYC breakapart probe: two patients (1.9%) with cryptic MYC/IGH fusion (finally diagnosed as BL) and 10 patients (9.3%) with 11q gain/loss (finally diagnosed as Burkitt-like lymphoma with 11q aberration). The exact breakpoints of the cryptic MYC/IGH were investigated by next-generation sequencing. The MYC insertions' breakpoints were identified in PVT1 in the first case, and 42 kb upstream of 5'MYC in the second case. To date, a molecular characterization of the MYC insertion in BL has only been reported in one case. Detailed descriptions of our MYC insertions in a routinely and consecutively diagnosed suspBL cohort will contribute to resolving the issue of MYC negativity in BL. In our opinion, the presence of the MYC insertions in BL and other lymphomas might be underestimated, because routine genetic diagnostics are usually based on FISH only, without karyotyping.

Genetic progression of post-transplant Burkitt-like lymphoma case with 11q-Gain/Loss and MYC amplification.

"Burkitt-like lymphoma with 11q aberration" is a new provisional entity in the latest revision of lymphoma's World Health Organization classification described as carrying the specific 11q-gain/loss aberration and lacking MYC rearrangement. Morphologically, phenotypically and by gene and microRNA expression profiling these lymphomas resemble Burkitt lymphoma. The 11q-gain/loss was also found in post-transplant patients with molecular Burkitt lymphoma signature without MYC rearrangement. Recent reports describe aggressive lymphomas with coexistence of 11q-gain/loss and MYC rearrangement. In this report we describe post-transplant Burkitt-like lymphoma with 11q aberration and MYC amplification. Genetic studies were conducted at two time points: before therapy and during progression. In both cytogenetic examinations, peculiar 11q-gain/loss was detected. Percentage of cells carrying MYC amplification increased from 2% at initial diagnosis to 97% during progression. The MYC amplification can functionally correspond to MYC translocation and to MYC overexpression. The presence of MYC amplification seems to increase the aggressiveness of the reported disease course, so even a small clone with this change should be indicated in cytogenetic result.

Clinical importance of the EMSY gene expression and polymorphisms in ovarian cancer.

EMSY, a BRCA2-associated protein, is amplified and overexpressed in various sporadic cancers. This is the first study assessing the clinical impact of its expression and polymorphisms on ovarian cancer (OvCa) outcome in the context of the chemotherapy regimen used. In 134 frozen OvCa samples, we assessed EMSY mRNA expression with Reverse Transcription-quantitative PCR, and also investigated the EMSY gene sequence using SSCP and/or PCR-sequencing. Clinical relevance of changes in EMSY mRNA expression and DNA sequence was evaluated in two subgroups treated with either taxane/platinum (TP, n=102) or platinum/cyclophosphamide (PC, n=32). High EMSY expression negatively affected overall survival (OS), disease-free survival (DFS) and sensitivity to treatment (PS) in the TP-treated subgroup (p-values: 0.001, 0.002 and 0.010, respectively). Accordingly, our OvCa cell line studies showed that the EMSY gene knockdown sensitized A2780 and IGROV1 cells to paclitaxel. Interestingly, EMSY mRNA expression in surviving cells was similar as in the control cells. Additionally, we identified 24 sequence alterations in the EMSY gene, including the previously undescribed: c.720G>C, p.(Lys240Asn); c.1860G>A, p.(Lys620Lys); c.246-76A>G; c.421+68A>C. In the PC-treated subgroup, a heterozygous genotype comprising five SNPs (rs4300410, rs3814711, rs4245443, rs2508740, rs2513523) negatively correlated with OS (p-value=0.009). The same SNPs exhibited adverse borderline associations with PS in the TP-treated subgroup. This is the first study providing evidence that high EMSY mRNA expression is a negative prognostic and predictive factor in OvCa patients treated with TP, and that the clinical outcome may hinge on certain SNPs in the EMSY gene as well.

A case of primary testicular germ cell tumor with rhabdomyosarcoma metastases as an example of applying the FISH method to diagnostic pathology.

We present the interesting case of a 38-year-old man with a primary malignant tumor of the right testis that metachronously metastasized to the urinary bladder and the stomach. Histologically, the testicular tumor was a mixed germ cell tumor composed of teratoma and embryonal carcinoma, but it also contained a sarcoma component of somatic type malignancy. Metastases showed rhabdomyoblastic differentiation histologically identical to the sarcoma component of the testicular tumor that was diagnosed as rhabdomyosarcoma. By applying fluorescence in situ hybridization (FISH) to the cytogenetic examination of cells taken from the periventricular lymph node metastases, we demonstrated a structural chromosomal aberration characteristic of testicular neoplasms, i.e. the presence of isochromosome 12p (i(12p)). Additionally, the diagnosis was supported by immunohistochemistry.

Complete cytogenetic and molecular response after imatinib treatment for chronic myeloid leukemia in a patient with atypical karyotype and BCR-ABL b2a3 transcript.

The molecular hallmark of CML is the BCR-ABL fusion gene, usually with specific breakpoints within ABL intron 1 and BCR introns b2, b3, and e19. The amplification of the BCR-ABL hybrid gene resulting from additional copies of the Ph chromosome has been identified as a mechanism for imatinib (IM) resistance. Cytogenetic clonal evolution correlates with the accelerated phase of leukemia, whereas deletions in the derivative chromosome 9 are associated with a poor prognosis. Relevance in IM therapy is unclear. We report a case of a 39-year-old male with chronic phase CML. Cytogenetic studies showed a complex karyotype with additional copies of the Ph chromosome, sextasomy 8, and ASS gene deletion. An unusual aberrant fusion gene product was derived from the joining of BCR exon 13 (b2) and ABL exon 3 (a3). During IM treatment, the patient was monitored in 3- to 6-month intervals. Major cytogenetic response was achieved after 5 months; complete cytogenetic and molecular remission was reached after 8 months; after 22 months, normal karyotype and absence of the BCR-ABL product continued. Our data seem to confirm the data of others in regards to the b2a3 breakpoint, suggesting a better prognosis, regardless of other unfavorable factors.

Variant t(2;11)(p11.2;q13) without IGK involvement in a case of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is characterized by the t(11;14)(q13;q32) translocation, which leads to overexpression of the cyclin D1 (CCND1) gene. This translocation is observed in almost all cases of MCL. In this alteration, the involvement of immunoglobulin heavy chain (IGH) locus plays a key role in the activation of the CCND1 oncogene. Translocations affecting IGH loci are mostly prevalent in B-cell lymphomas, but variant translocations involving immunoglobulin kappa (IGK) or lambda (IGL) light chain loci have been observed in a minority of B-lymphoid malignancies. Variant translocations have been reported in only a few cases of MCL, however. This report presents a case of MCL with a variant t(2;11)(p11.2;q13), rearrangement of the CCND1 gene, and overexpression of cyclin D1. To characterize this rearrangement, specific noncommercial probes were used. This set of probes comprises IGK and REL flanking probes and 12 bacterial artificial chromosome (BAC) probes covering the region to be investigated. The results indicated that this alteration has not affected the IGK locus, and the breakpoint was within a 260-kb region located approximately 1 Mb telomerically to the IGK gene. It is probable that the KV3J gene localized in this region could deregulate the expression of cyclin D1.

The 11q-Gain/Loss Aberration Occurs Recurrently in MYC-Negative Burkitt-like Lymphoma With 11q Aberration, as Well as MYC-Positive Burkitt Lymphoma and MYC-Positive High-Grade B-Cell Lymphoma, NOS.

OBJECTIVES: The latest revision of lymphoma's World Health Organization classification describes the new provisional entity "Burkitt-like lymphoma with 11q aberration" (BLL, 11q) as lacking MYC rearrangement, but harboring the specific11q-gain/loss aberration. We report genetic characteristics of 11 lymphoma cases with this aberration. METHODS: Classical cytogenetics, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism/array comparative genomic hybridization. RESULTS: The 11q aberrations were described as duplication, inversion, and deletion. Array comparative genomic hybridization showed two types of duplication: bigger than 50 megabase pairs (Mbp) and smaller than 20 Mbp, which were associated with bulky tumor larger than 20 cm and amplification of the 11q23.3 region, including KMT2A. Six cases revealed a normal FISH status of MYC and were diagnosed as BLL,11q. Five cases showed MYC rearrangement and were diagnosed as Burkitt lymphoma (BL) or high-grade B-cell lymphoma, not otherwise specified (HGBL, NOS). CONCLUSIONS: The 11q-gain/loss is not specific for BLL, 11q, but occurs recurrently in MYC-positive BL and MYC-positive HGBL.

Chromosome 1 amplification has similar prognostic value to del(17p13) and t(4;14)(p16;q32) in multiple myeloma patients: analysis of real-life data from the Polish Myeloma Study Group.

The study aimed to assess prognostic significance of del(13q14), del(17p13), t(4;14)(p16;q32), and amp(1q21) in newly diagnosed myeloma patients treated mostly with thalidomide-based therapies. All genetic abnormalities except del(13q14) were independent prognostic factors associated with shortened progression-free survival (PFS) and overall survival (OS). Patients with no abnormalities, one abnormality, and ≥2 abnormalities had a median PFS of 41.8, 17.0, and 10.0 months, respectively; a median OS was not reached, 48.0 and 23.3 months, respectively. According to the presence of amp(1q21), t(4;14)(p16;q32), and del(17p13) and the International Staging System (ISS), we stratified patients into low-risk, intermediate-risk and high-risk groups. A median PFS was 52.9, 25.6, and 10.0 months, respectively; a median OS was not reached, 64.0 and 25.0 months, respectively. In conclusion, our study confirmed the prognostic value of cytogenetic changes and showed that prognostic models based on ISS and cytogenetic studies should include not only del(17p13) and t(4;14)(p16;q32), but also amp(1q21).

Concomitance of monosomal karyotype with at least 5 chromosomal abnormalities is associated with dismal treatment outcome of AML patients with complex karyotype - retrospective analysis of Polish Adult Leukemia Group (PALG).

Monosomal karyotype (MK) and complex karyotype (CK) are poor prognostic factors in acute myeloid leukemia (AML). A comprehensive analysis of cytogenetic and clinical factors influencing an outcome of AML-CK+ was performed. The impact of cladribine containing induction on treatment results was also evaluated. We analyzed 125 patients with AML-CK+ treated within PALG protocols. MK was found in 75 (60%) individuals. The overall complete remission (CR) rate of 66 intensively treated patients was 62% vs. 28% in CK+ MK- and CK+ MK+ group (p = .01). No difference in CR rate was observed between DA and DAC arms. The overall survival (OS) in intensively treated patients was negatively influenced by MK, karyotype complexity (≥5 abnormalities), and WBC >20 G/L in multivariate analysis. The addition of cladribine to DA regimen improved OS only in MK- but not in MK+ group. In conclusion, concomitance of MK with ≥5 chromosomal abnormalities is associated with dismal treatment outcome in AMK-CK+.

Unusual IgD+/CD38-follicular lymphoma with leukemic presentation.

Follicular lymphoma (FL) is a low-grade lymphoma, with rare presentation of leukemic phase in peripheral blood at the diagnosis. We describe a 49-yr-old woman who developed leukemic phase of FL in a 3 mo period after histological diagnosis of peripheral lymph node. To confirm the final diagnosis, flow cytometry (FCM) of peripheral blood, nested PCR with bcl-2 rearrangement, and cytogenetic analysis of peripheral blood and bone marrow cells were done. Lymphoma cells were negative for CD38 and expressed monoclonal surface immunoglobulins with relatively strong and "bright" IgD and "dim" kappa-chain by FCM analysis. Although the patient presented with generalized lymphadenopathy, massive peripheral blood and bone marrow involvement, she achieved complete clinical response after first-line chemotherapy COP and rituximab. She is still in a good condition with follow up over 2 yr.