High-grade transformation in splenic marginal zone lymphoma with circulating villous lymphocytes: the site of transformation influences response to therapy and prognosis.

In a series of 48 patients with splenic marginal zone lymphoma (SMZL) with circulating villous lymphocytes, we describe the clinical and laboratory features of nine cases that transformed to high-grade B-cell lymphoma. These patients had a significantly greater incidence of peripheral lymph node involvement at diagnosis when compared to SMZL patients who did not transform (P < 0.03). While transformation in the bone marrow is frequently refractory to therapy and associated with poor outcome in SMZL, lymph node transformation responds well to chemotherapy with durable progression-free and overall survival.

Assessment of fludarabine plus cyclophosphamide for patients with chronic lymphocytic leukaemia (the LRF CLL4 Trial): a randomised controlled trial.

BACKGROUND: Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide. We aimed to establish whether this treatment combination provided greater survival benefit than did chlorambucil or fludarabine. METHODS: 777 patients with chronic lymphocytic leukaemia requiring treatment were randomly assigned to fludarabine (n=194) or fludarabine plus cyclophosphamide (196) for six courses, or chlorambucil (387) for 12 courses. The primary endpoint was overall survival, with secondary endpoints of response rates, progression-free survival, toxic effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number NCT 58585610. FINDINGS: There was no significant difference in overall survival between patients given fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Complete and overall response rates were better with fludarabine plus cyclophosphamide than with fludarabine (complete response rate 38%vs 15%, respectively; overall response rate 94%vs 80%, respectively; p<0.0001 for both comparisons), which were in turn better than with chlorambucil (complete response rate 7%, overall response rate 72%; p=0.006 and 0.04, respectively). Progression-free survival at 5 years was significantly better with fludarabine plus cyclophosphamide (36%) than with fludarabine (10%) or chlorambucil (10%; p<0.00005). Fludarabine plus cyclophosphamide was the best combination for all ages, including patients older than 70 years, and in prognostic groups defined by immunoglobulin heavy chain gene (V(H)) mutation status and cytogenetics, which were tested in 533 and 579 cases, respectively. Patients had more neutropenia and days in hospital with fludarabine plus cyclophosphamide, or fludarabine, than with chlorambucil. There was less haemolytic anaemia with fludarabine plus cyclophosphamide (5%) than with fludarabine (11%) or chlorambucil (12%). Quality of life was better for responders, but preliminary analyses showed no significant difference between treatments. A meta-analysis of these data and those of two published phase III trials showed a consistent benefit for the fludarabine plus cyclophosphamide regimen in terms of progression-free survival. INTERPRETATION: Fludarabine plus cyclophosphamide should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.

Prolymphocytic leukaemia of B- and T-cell subtype: a state-of-the-art paper.

Prolymphocytic leukaemias of B and T cell subtype are rare diseases. Despite recent advances in immunophenotyping and molecular cytogenetics, leading to a better understanding of the underlying cell biology of the prolymphocytic leukaemias, prognosis for these patients remains poor. Purine analogues and monoclonal antibodies have shown efficacy in B-cell prolymphocytic leukaemia although further studies are warranted. Monoclonal antibody therapy with alemtuzumab has significantly improved outcome in T-cell prolymphocytic leukaemia (T-PLL) but responses are still transient and further disease progression is inevitable. While allogeneic stem cell transplant is an attractive option, due to the older age group of T-PLL patients the morbidity and mortality associated with the procedure is significant.

The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms.

Over the last decade, there has been a significant body of information regarding the biology of the lymphoid neoplasms. This clearly supports the need for updating the 2008 WHO (World Health Organization) classification of haematopoietic and lymphoid tumours. The 2017 WHO classification is not a new edition but an update and revision of the 4th edition. New provisional entities but not new definitive entities are included, and novel molecular data in most of the entities and changes in the nomenclature in few of them have been incorporated. In the context of the mature T- and NK-cell neoplasms, the most relevant updates concern to: 1-dysregulation of the JAK/STAT pathway due to gene mutations which are common to various aggressive and indolent neoplasms; 2-incorporation of new molecular players that are relevant to the pathogenesis of these neoplasms and/or have prognostic implications; 3-inclusion of new provisional entities within the subgroups of anaplastic, primarily intestinal and cutaneous lymphomas such as breast implant-associated anaplastic large cell lymphoma, indolent T-cell lymphoproliferative disorder of the gastrointestinal tract and primary cutaneous acral CD8+ T-cell lymphoma; 4-identification of poor prognostic subtypes of peripheral T-cell lymphomas not otherwise specified (PTCL, NOS) characterized by overexpression of certain genes and of a subgroup PTCL, NOS with a T follicular phenotype that now is included together with angioimmunoblastic T-cell lymphoma under the umbrella of lymphomas with a T follicular helper phenotype; and 5-refinement on the designation and definition of already established entities. A review of the major changes will be outlined.

Microsatellite instability indicative of defects in the major mismatch repair genes is rare in patients with B-cell chronic lymphocytic leukemia: Evaluation with disease stage and family history.

A possible role for DNA mismatch repair defects and microsatellite instability (MSI) in the pathogenesis of a number of B-cell lymphoproliferative disorders has recently been debated. To gain further insight into the impact of MSI on B-CLL, we evaluated samples from a series of 982 patients using the mono-satellite markers BAT25 and BAT26, which are highly sensitive in demonstrating classical mismatch repair (MMR) deficiency. Only 1% of cases displayed MSI and this was not correlated with stage of disease or family history of B-CLL. A sub-polymorphic germline variant of BAT25 was identified in one familial case, which was also detected in the patient's affected brother. In conclusion, our study demonstrates that MSI does not have a prominent role in the pathogenesis of B-CLL.

IgVH genes mutation and usage, ZAP-70 and CD38 expression provide new insights on B-cell prolymphocytic leukemia (B-PLL).

B-prolymphocytic leukemia (B-PLL) is a rare disease with poor prognosis. To further characterize the biological features of this disease, we analyzed immunoglobulin heavy chain (IgVH) mutations, ZAP-70 and CD38 in 19 cases with de novo B-PLL. Immunoglobulin heavy chain genes analysis showed an unmutated pattern (>98% homology to germ line) in 9/17 cases (53%), with 100% homology in eight. In the remaining, it ranged from 90 to 97.4%, with three cases slightly mutated (98-95%) and five heavily mutated (<95%). All B-PLL utilized members of VH3 (11/17) and VH4 (6/17) families, with V3-23, V4-59 and V4-34 gene accounting for more than half of them, regardless of mutational status. ZAP-70, assessed by flow cytometry, ranged from 1 to 91% cells, being > or =20% in 57% of cases. CD38 ranged from 1 to 99% (median 21%). There was no correlation between IgVH status and ZAP-70 or CD38 expression, but male gender and del(17p) were more common in the unmutated group. Neither IgVH mutations, CD38 expression nor del(17p) influenced patients' outcome. Unexpectedly, ZAP-70+ B-PLL patients survived longer (40 months) than ZAP-70- B-PLL (8 months). B-PLL appears biologically heterogeneous regarding IgVH mutations, ZAP-70 and CD38 expression, showing a pattern distinct from that of other lymphoproliferative disorders.

Molecular cytogenetic analysis in splenic lymphoma with villous lymphocytes: frequent allelic imbalance of the RB1 gene but not the D13S25 locus on chromosome 13q14.

Structural abnormalities of chromosome 13q are one of the most frequent genetic aberrations in human tumors. 13q rearrangements are, however, infrequent in splenic lymphoma with villous lymphocytes (SLVL) by karyotype analysis. We have investigated the incidence of 13q14 deletions in a series of 74 SLVL cases by interphase fluorescence in situ hybridization using unique sequence probes for the RB1 and the D13S25 loci, which are frequently deleted in chronic lymphocytic leukemia. Chromosome 12 was also evaluated by fluorescence in situ hybridization using a pericentromeric DNA probe. 13q14 deletion was detected in 37 of 74 (50%) tumors. Thirty-five cases (47%) exhibited monoallelic loss of RB1, and 9 (12%) showed hemizygous D13S25 deletion. Seven cases displayed coexistence of RB1 and D13S25 deletion. Trisomy 12 was detected in 2 of 74 (3%) tumors. G-banding analysis in 40 tumors showed no interstitial deletion of 13q14 in any case. In contrast with the molecular findings observed in chronic lymphocytic leukemia, our results indicate that trisomy 12 is an uncommon chromosomal aberration in SLVLs, and microdeletion of 13q14 at the RB1 locus but not D13S25 is a frequent and specific genetic event in this disease, suggesting that allelic loss of the RB1 gene may play a role in the pathogenesis of SLVL.

ATM is usually rearranged in T-cell prolymphocytic leukaemia.

T-prolymphocytic leukaemia (T-PLL) is a rare, sporadic leukaemia similar to a mature T-cell leukaemia seen in some patients with Ataxia Telangiectasia (A-T), a recessive multisystem disorder caused by mutations of the ATM gene at chromosome 11q23. ATM sequence mutations have been reported in 46% of T-PLL cases, but some cases also have karyotypic abnormalities at 11q, including 11q23. This led us to investigate the structure of the ATM locus in a panel of eight cases, two of which had 11q23 abnormalities. As expected, nucleotide changes were detected in some samples. Two remission samples were wild type. To test for structural lesions, DNA fibres were hybridized with a contig of four labelled cosmids spanning the ATM locus. In all samples there were structural lesions and in four samples both alleles were affected. This provides strong evidence for our suggestion that ATM acts as a tumour suppressor during T-PLL tumorigenesis. Some additional role for ATM during T-PLL tumorigenesis is possible since nucleotide changes were present in addition to structural lesions disrupting both alleles. The mechanism of inactivation appeared to be unusual because multiple structural lesions on one allele were often observed.

The role of pentostatin in the treatment of T-cell malignancies: analysis of response rate in 145 patients according to disease subtype.

PURPOSE: To assess the results of treatment with the purine analog 2'deoxycoformycin (pentostatin [DCF]) in patients with postthymic T-cell malignancies. PATIENTS AND METHODS: One hundred forty-five patients with postthymic T-cell malignancies were given DCF intravenously at 4 mg/m2/wk for the first 4 weeks and then every 2 weeks until maximal response; the last 30 patients received weekly injections until maximal response. RESULTS: The overall response rate was 32% (complete responses [CRs] plus partial responses [PRs]), with marked variation according to diagnosis. The best responses occurred in patients with Sézary syndrome (62%) and T-prolymphocytic leukemia (T-PLL) (45%), with CRs in three of 16 Sézary syndrome and five of 55 T-PLL patients. In contrast, no responses (NRs) were documented in 13 patients with other types of cutaneous T-cell lymphoma, including five mycosis fungoides. Two of five patients with large granular lymphocyte (LGL) leukemia had a CR and two of four with Sézary cell leukaemia had a PR. A low response rate was observed in 27 patients with peripheral T-non-Hodgkin's lymphoma (T-NHL) (19%) and in 25 with adult T-cell leukemia/lymphoma (ATLL) (12%). The latter included two CRs and one PR. Toxicity was low and DCF was generally well tolerated. No significant differences were observed when results were analyzed according to previous treatment. Disease subtype was the most important factor to influence results. CONCLUSION: We conclude that DCF is effective as a single agent in T-PLL, Sézary syndrome, and LGL leukemia, but has low activity in other T-cell disorders.

Treatment of T-cell prolymphocytic leukemia with human CD52 antibody.

PURPOSE: T-prolymphocytic leukemia (T-PLL) is an aggressive malignancy of mature T cells refractory to conventional chemotherapy, with a median survival duration of 7.5 months. We report here promising results with the use of a genetically reshaped human CD52 antibody, CAMPATH-1H. PATIENTS AND METHODS: Fifteen patients with T-PLL, most of whom had received the purine analog deoxycoformycin (DCF), were treated with CAMPATH-1H. Results were compared with those of 25 patients treated with DCF. RESULTS: Major responses occurred in 11 patients (73%) treated with CAMPATH-1H compared with 40% with DCF. Complete remissions (CRs) were documented in nine (60%) of the CAMPATH-1H cases and only three (12%) were obtained with DCF. CRs with CAMPATH-1H were durable, and re-treatment with the antibody resulted in second CRs in three relapsed patients. Two of them were successfully autografted with peripheral-blood and bone marrow stem cells collected during the first CR. Apart from first-dose reactions, infusions of CAMPATH-1H were well tolerated. However, two responding patients developed severe bone marrow aplasia that was fatal in one; the second remained moderately pancytopenic 21 weeks after stopping CAMPATH-1H therapy. The cause of this adverse effect is unknown. CONCLUSION: CAMPATH-1H is an effective agent in T-PLL and represents a significant improvement over other types of therapy. However, CAMPATH-1H alone is not sufficient for long-term remissions, and the role of autologous stem-cell transplantation needs further investigation.

Richter's transformation of chronic lymphocytic leukemia. The possible role of fludarabine and the Epstein-Barr virus in its pathogenesis.

Transformation of CLL into a large cell lymphoma has an incidence of 3-5%. We have studied 101 cases of CLL treated with fludarabine over a 10-year period (1990-2000) and observed a 12% incidence of transformation. In six of 12 patients, transformation was documented within 4 months following treatment with fludarabine. Pathological material, available in nine cases, was investigated for latent EBV by staining for LMP-1 by immunohistochemistry and EBERs-1 and 2 by in situ hybridisation. LMP-1 and EBERs were demonstrated in three of the nine samples. In two cases there was a different pattern of immunoglobulin gene rearrangement in the transformed cells assessed by PCR (FR3 fragment) compared to the original CLL clone. One of these two cases showed evidence of latent EBV. The other seven cases, of which two were EBV positive, showed identical pattern of Ig gene rearrangement in both the CLL and the transformed cells. We suggest that the relatively high incidence of transformation in this series may be due to immunosuppression mainly related to fludarabine, although other agents and prior therapies may have also contributed.

Prolonged treatment response in aggressive natural killer cell leukemia.

We describe a case of natural killer (NK) cell leukemia with acute presentation, systemic symptoms and hepatosplenomegaly. The uniform and aberrant phenotype of NK cells with infiltration of bone marrow and spleen was in keeping with a malignant diagnosis. Aggressive presentation was demonstrated by marked constitutional symptoms and significant tumor burden (liver, spleen, blood, bone marrow). The subsequent clinical course has been indolent, but this may have been influenced by treatment. Treatment consisted sequentially of splenectomy, intravenous pentostatin and the combination of cyclosporine A and recombinant human erythropoietin and has resulted in survival of over 48 months. We discuss the difficulties in the diagnosis of this condition, explore possible causes of cytopenia(s), and highlight the role of immunosuppression in controlling disease manifestations in large granular lymphocyte proliferative disorders.

CD52 expression in T-cell large granular lymphocyte leukemia--implications for treatment with alemtuzumab.

Few reports on the successful treatment of T-cell large granular lymphocyte (LGL) leukemia with the humanized anti-CD52 monoclonal antibody alemtuzumab are emerging in the literature. The expression of CD52 by LGLs has not been previously investigated. Using semi-quantitative 2- and 3-color flow cytometry, we documented the expression of CD52 in 100% of abnormal cells in T-cell LGL leukemia (n = 11) and natural killer (NK) cell LGL leukemia (n = 2), and showed no significant difference in CD52 expression between T-cell prolymphocytic leukemia (PLL) and T-cell LGL leukemia. Higher CD52 expression has been noted in responders to alemtuzumab in T-cell PLL and in chronic lymphocytic leukemia (CLL), a B-cell disorder. The strong and consistent expression of CD52 shown here highlights the potential role of alemtuzumab in the treatment of refractory T-cell LGL leukemia and possibly aggressive NK cell leukemia.

The classification of acute leukaemia.

The standard methods for classifying acute leukaemias now include morphology, cytochemistry and membrane markers. Major advances in immunology, in particular the development of monoclonal antibodies (McAb) with lineage specificity, have provided objective positive criteria for the diagnosis of acute lymphoblastic leukaemia (ALL). The FAB group has recognised the importance of McAb for the classification of some forms of acute myeloid leukaemia (AML), such as megakaryoblastic leukaemia, AML-M7, in which reactivity with McAb against platelet glycoproteins is a requirement for diagnosis. More recently the group has defined a type of myeloblastic leukaemia with minimal differentiation, AML-MO, in which myeloid cytochemistry is negative and the diagnosis is made by the expression of myeloid antigens and negative lymphoid markers in the blast cells. However, new problems have emerged with the wider use of McAb which now need to be addressed: the most important is the precise evaluation criteria for biphenotypic leukaemia for which we have proposed a scoring system in order to recognise the genuine cases which constitute a distinct disease entity. The role of karyotyping in the classification of acute leukaemia is gradually being defined (MIC proposals) and some forms of acute leukaemia can only be diagnosed by chromosome translocations, e.g. Ph+ ALL, resulting from t(9;22) and t(4;11) in infant ALL. Several translocations can also be demonstrated by molecular techniques. Cases with t(8;16) (p11;p13) are characterised by myelomonocytic features, erythrophagocytosis and fibrinolysis and represent a type of AML which can be defined primarily by its cytogenetic abnormality.

Monoclonal antibody Ki-67 identifies B and T cells in cycle in chronic lymphocytic leukemia: correlation with disease activity.

Ki-67 is a monoclonal antibody that recognises a nuclear antigen expressed during most phases of the cell cycle. We have analysed, by immunocytochemistry, the frequency, morphology, and clinical significance of Ki-67+ cells in 108 patients with B-cell chronic lymphocytic leukemia (CLL). Because in normal peripheral blood Ki-67+ cells are mainly T lymphocytes, we have also investigated, by double immunoenzymatic staining, the proportion of Ki-67+ T cells (Ki-67/CD3+) in CLL. Four groups of patients were identified: (i) 47 with stage A, (ii) 32 with stages B + C, (iii) 24 with greater than 10% of circulating prolymphocytes (CLL/PL) and (iv) five with Richter's syndrome. Within stage A CLL, two groups were considered: A' (Hb greater than or equal to 12 g/dl and lymphocytes less than 30 + 10(9)/l) and A" (Hb less than 12 g/dl or lymphocytes greater than or equal to 30 x 10(9)/l). The percentage and absolute number of Ki-67+ leukemic cells was found to increase with the stage of the disease and correlate with the proportion of prolymphocytes. On the other hand, the proportion of Ki-67+ T cells (CD3+) was significantly higher in patients with CLL stage A' (29.3 +/- 4.5), which includes patients with long-standing, stable disease, than in CLL stage A" (9.5 +/- 3.3), B + C (7.1 +/- 4.6), and CLL/PL (6.4 +/- 2.8). Ki-67 seems to identify patients with more aggressive forms of CLL, such as CLL/mu 2PL with more than 10% Ki-67+ cells (25% of the cases) and Richter's syndrome, in which all the large lymphoma cells are Ki-67+. Long-term follow-up will establish whether Ki-67 is a good prognostic marker and can predict disease outcome.

Lineage commitment in biphenotypic acute leukemia.

Acute leukemias (ALs) with phenotypic and genotypic features of several hematopoietic lineages are difficult to classify and may represent the transformation of multipotent stem cells. We have studied immunological features of 200 cases of acute leukemia (109 acute myelogenous leukemia, AML, and 91 acute lymphoblastic leukemia, ALL, according to FAB criteria), including 17 (8.5%) classified as biphenotypic by a scoring system based on the number and specificity of unexpected lineage antigens and which gives more weight to cytoplasmic markers such as myeloperoxidase, CD3, and CD22, and less to other membrane markers. Sixty-eight AML and 42 ALL cases were also examined for rearrangements of the immunoglobulin (Ig) and T-cell receptor (TCR) beta, gamma, and delta genes, and these included 12 biphenotypic AL. The expression of myeloid antigens in ALL was seen in 25% of the cases. All B-lineage ALL had rearrangements and/or deletions of the Ig genes whereas TCR beta, gamma, and delta genes were rearranged in 21%, 52%, and 71%, respectively. TCR delta, gamma and/or beta were rearranged in T-ALL and four out of 13 cases had Ig gene rearrangement. Lymphoid-associated antigens were expressed in 40% of AML cases; those most frequent expressed were CD7 (17%), CD2 (15%), CD19 (10%), and CD10 (7.5%). Evidence of Ig and/or TCR gene rearrangements was detected in 12% of AML cases. There was no correlation between the isolated expression of terminal deoxynucleotidyl transferase (TdT), B, and T-cell antigens with Ig and TCR gene rearrangements. However, in cases of AML defined as biphenotypic because they expressed two or more lymphoid antigens there was a statistically significant correlation between gene rearrangements and lymphoid score (p < 0.001). Our findings support the concept of biphenotypic leukemia as a distinct entity in which there is frequent correspondence between phenotypic and genotypic changes.

Differential TdT expression in acute leukemia by flow cytometry: a quantitative study.

Terminal deoxynucleotidyl transferase (TdT) has long been considered a diagnostic marker for acute lymphoblastic leukemia. Reports of TdT-positive cells in acute myeloid leukemia have lately questioned its diagnostic value. TDT has been detected mainly by microscopy methods: immunofluorescence and immunocytochemistry. The aim of this study was to reevaluate the diagnostic importance of TdT in acute leukemia by using flow cytometry with a method that allows quantitative analysis. Fifty-eight cases of acute leukemia were studied and TdT expression was quantified using calibrated fluorescent beads. The highest TdT values were found in B lineage acute lymphoblastic leukemia (ALL) while acute myeloid leukemia (AML) had the lowest values, even in cases with a high percentage of TdT-positive cells. Biphenotypic leukemia had intermediate values between B-lineage and T-lineage acute leukemia. The difference between these groups was statistically significant (P < 0.0001). The TdT assay by flow cytometry was more precise than immunocytochemistry because it recognizes quantitative differences between ALL and AML. It is also valuable in better defining the maturation stages in pre-B ALL and T-ALL. We conclude that quantitative flow cytometry of TdT re-establishes the diagnostic value of this enzyme and has potential applications for the study of minimal residual disease.

Differential expression of c-myc protein in B and T lymphocytes.

Overexpression of c-myc may play a role in the multistep pathogenesis of B- and T-cell malignancies. To determine whether this expression is inappropriate requires information on the normal cellular counterparts. There is no agreement in the literature on the levels of expression of c-myc mRNA and protein in normal peripheral blood lymphocytes and there are no reports on the differential expression in different lymphocyte populations. The aim of this study was to assess the state of c-myc expression in normal peripheral blood lymphocytes at the single cell level by immunocytochemistry and flow cytometry. Two monoclonal antibodies against c-myc and specific peptide inhibition controls were tested in mononuclear cells from nine healthy volunteers and the HL60 cell line. The expression of c-myc in B- and T-lymphocyte subsets was studied by two-colour immunocytochemistry and flow cytometry. Using calibrated reference standards, we quantified the c-myc protein and results were referred as molecules of equivalent soluble fluorochrome. Almost all lymphocytes express c-myc by both techniques. Two patterns of nuclear staining (weak and strong) were found by immunocytochemistry and this was confirmed by two peaks of fluorescence intensity by flow cytometry. Double immunostaining showed that the stronger pattern of c-myc staining corresponds to B lymphocytes and the weak one to T cells. Quantification confirmed these results which demonstrated a statistically significant difference in the expression of c-myc in these two lymphocyte populations (p < 0.005). Our results demonstrate for the first time that normal circulating B cells express higher levels of c-myc protein than T lymphocytes.

A t(8;14)(q24;q32) in a T-lymphoma/leukemia of CD8+ large granular lymphocytes.

Chromosome studies in a case of T cell lymphoma/leukemia, in which a high proportion of the dividing cells had a t(8;14)(q24;q32) similar to that seen in Burkitt's lymphoma, are described. The tumor cells had a mature T cell phenotype (TdT-,CD3+,CD8+,CD4-) and were morphologically large granular lymphocytes and immunoblasts, both cell types with similar lysosomal granules in the cytoplasm. The immunoglobulin heavy chain gene and the T cell receptor beta chain gene were not rearranged, while the T cell receptor gamma chain gene was polyclonally rearranged. Mitoses were obtained only from spontaneously dividing cells in the absence of mitogens; 49 of the 50 metaphases analyzed were chromosomally abnormal and had a t(1;22)(q12;q13) and dup(1)(q31q32) in all of them; 48 metaphases had in addition a t(8;14)(q24;q32) which presumably arose during clonal evolution. The latter may be associated with the aggressive behavior of this T cell disorder by comparison with other proliferations of large granular lymphocytes. Although abnormalities involving 14q32 are characteristic of B cell disorders, they have also been described in T cell malignancies, suggesting that genes transcribed in T cells and/or oncogenic sequences significant in T cell neoplasia are present in 14q32.