[Eosinophilia induced by parasitic infection].
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Diagnosis, Differential↗
Biomedical subjects
T Otsuki
Publications and source records attributed to T Otsuki.
Tyrosine residues 239 and 240 of Shc are phosphatidylinositol 4,5-bisphosphate-dependent phosphorylation sites by c-Src.
In the previous study (Sato K.-I. et al. (1997) FEBS Lett. 410, 136-140), we showed that the phosphorylation of Shc protein by c-Src is dependent on the binding of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) to the PTB domain of Shc. In this study, we demonstrate that, in contrast to c-Src, v-Src and epidermal growth factor (EGF) receptor can phosphorylate Shc in a PtdIns(4,5)P2-independent manner and at different phosphorylation sites. To determine the phosphorylation sites in Shc, we used mutant Shc proteins in which tyrosine residues (Y) 317 and/or 239 and 240 were replaced by phenylalanine residues (F). We found that Y317F Shc but not Y239/240F or Y239/240/317F Shc was phosphorylated by c-Src. The reaction was PtdIns(4,5)P2-dependent and inhibited by the addition of PTB domain of Shc. On the other hand, v-Src and EGF receptor were able to phosphorylate both Y317F and Y239/240F but not Y239/240/317F Shc in a PtdIns(4,5)P2-independent manner. These results highlight the difference between c-Src and v-Src or EGF receptor and suggest that c-Src can phosphorylate predominantly on Tyr239/240 of Shc only when Shc PTB domain is bound to PtdIns(4,5)P2.
Adaptor Proteins, Signal Transducing↗
A novel chromosomal translocation t(4; 14)(p16.3; q32) in multiple myeloma involves the fibroblast growth-factor receptor 3 gene.
Chromosomal translocations involving the immunoglobulin heavy chain (IGH) locus at chromosome 14q32 represent a common mechanism of oncogene activation in lymphoid malignancies. In multiple myeloma (MM), the most consistent chromosomal abnormality is the 14q+ marker, which originates in one third of cases through a t(11; 14)(q13; q32) chromosomal translocation; in the remaining cases, the identity of the partner chromosomes has not been well established. We used a Southern blot approach based on the linkage analysis of the joining (J) and the constant (C) mu, alpha, and gamma regions to detect cases bearing IGH switch-mediated chromosomal translocations. We evaluated DNA of 88 nonkaryotyped patients with MM (78 cases) or plasma cell leukemia (PCL) (10 cases) and found the presence of "illegitimate" rearranged IGH fragments (no comigration between the J and C regions) in 21 cases. To confirm this analysis, we cloned the illegitimate rearranged fragments from three samples, and the molecular and fluorescent in situ hybridization (FISH) analyses indicated the presence of chromosomal translocations juxtaposing a switch IGH region to sequences from chromosomes 11q13 (one PCL case) or 4p16.3 (two MM cases). Interestingly, the breakpoints on 4p16.3 occurred about 14 kb apart in a genomic region located approximately 50 kb centromeric to the fibroblast growth-factor receptor 3 (FGFR3) gene. Moreover, Southern blot analysis using 4p16.3 genomic probes detected a rearrangement in an additional MM tumor. FISH analysis of the MM-derived KMS-11 cell line, reported to be associated with a t(4; 14)(p16.3; q32), showed that the FGFR3 gene was translocated on 14q32. High levels of FGFR3 mRNA expression were observed in the cloned MM tumors and KMS-11 cell line, but not in the cases that were apparently negative for this lesion. Furthermore, a point mutation at codon 373 in the transmembrane domain of the FGFR3 gene resulting in an amino acid substitution (Tyr --> Cys) was detected in the KMS-11 cell line. These findings indicate that the t(4; 14)(p16.3; q32) represents a novel, recurrent chromosomal translocation in MM, and suggest that the FGFR3 gene may be the target of this abnormality and thus contribute to tumorigenesis in MM.
Base Sequence↗
Ca2+ and its substitutes have two different binding sites and roles in soluble, quinoprotein (pyrroloquinoline-quinone-containing) glucose dehydrogenase.
To investigate the mode of binding and the role of Ca2+ in soluble, pyrroloquinoline-quinone (PQQ)-containing glucose dehydrogenase of the bacterium Acinetobacter calcoaceticus (sGDH), the following enzyme species were prepared and their interconversions studied: monomeric apoenzyme (M); monomer with one firmly bound Ca2+ ion (M*); dimer consisting of 2 M* (D); dimer consisting of 2 M and 2 PQQ (Holo-Y); dimer consisting of D with 2 PQQ (Holo-X); fully reconstituted enzyme consisting of Holo-X with two extra Ca2+ ions (Holo) or substitutes for Ca2+ (hybrid Holo-enzymes). D and Holo are very stable enzyme species regarding monomerization and inactivation by chelator, respectively, the bound Ca2+ being locked up in such a way that it is not accessible to chelator. D can be converted into M* by heat treatment and the tightly bound Ca2+ can be removed from M* with chelator, transforming it into M. Reassociation of M* to D occurs spontaneously at 20 degrees C; reassociation of M to D occurs by adding a stoichiometric amount of Ca2+. Synergistic effects were exerted by bound Ca2+ and PQQ, each increasing the affinity of the protein for the other component. Dimerization of M to D occurred with Ca2+, Cd2+, Mn2+, and Sr2+ (in decreasing order of effectiveness), but not with Mg2+, Ba2+, Co2+, Ni2+, Zn2+, or monovalent cations. Conversion of inactive Holo-X into active Holo, was achieved with Ca2+ or metal ions effective in dimerization. Although it is likely that activation of Holo-X involves binding of metal ion to PQQ, the spectral and enzymatic activity differences between normal Holo- and hybrid Holo-enzymes are relatively small. Titration experiments revealed that the two Ca2+ ions required for activation of Holo-X are even more firmly bound than the two required for dimerization of M and anchoring of PQQ. Although the two binding sites related with the dual function of Ca2+ show similar metal ion specificity, they are not identical. The presence of two different sites in sGDH appears to be unique because in other PQQ-containing dehydrogenases, the PQQ-containing subunit has only one site. Given the broad spectrum of bivalent metal ions effective in reconstituting quinoprotein dehydrogenase apoenzymes to active holoenzymes, but the limited spectrum for an individual enzyme, the specificity is not so much determined by PQQ but by the variable metal-ion-binding sites.
Acinetobacter calcoaceticus↗
Phosphatidylinositol 4,5-bisphosphate stimulates phosphorylation of the adaptor protein Shc by c-Src.
The adaptor protein Shc was prepared as glutathione S-transferase fusion proteins (GST-Shc) and used as in vitro substrate for c-Src. Since phosphotyrosine-binding domain of Shc has been shown to bind phosphatidyl-inositol 4,5-bisphosphate (PtdIns(4,5)P2) [Zhou et al. (1995) Nature 378, 584-592], effect of PtdIns(4,5)P2 on the phosphorylation of GST-Shc by c-Src was examined. PtdIns(4,5)P2 stimulated the phosphorylation of GST-Shc without any effect on the c-Src activity as judged by both its autophosphorylation and phosphorylation of exogenous substrate, Cdc2 peptide. On the other hand, phosphatidylserine, phosphatidic acid, phosphatidylinositol, and phosphatidylinositol 4-phosphate but not phosphatidylcholine stimulated the c-Src activity itself. Km for GST-Shc in the presence of 1 microM PtdIns(4,5)P2 was calculated to be 90 nM. The PtdIns(4,5)P2-dependent phosphorylation of GST-Shc was inhibited by a GST-fusion protein containing the phosphotyrosine-binding domain of Shc. These results suggest that PtdIns(4,5)P2 can act as a regulator of phosphorylation of Shc by c-Src through its binding to Shc.
3T3 Cells↗
Multiple cerebral infarctions in a patient with refractory idiopathic thrombocytopenic purpura.
Multiple cerebral infarctions were observed in a patient with refractory idiopathic thrombocytopenic purpura who was positive for lupus anticoagulant (LAC) when her platelet counts were 2000 microL-1. It is suspected that LAC may have played an important role in the pathogenesis of this patient's cerebral infarctions, although she had severe thrombocytopenia.
Adult↗
Elevated soluble Fas/APO-1 (CD95) levels in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours.
Soluble Fas (sFas) is produced as translation products of alternative mRNA splicing, and antagonizes the membranous Fas molecule in Fas/Fas ligand interactions. We investigated the serum sFas levels in 64 Japanese silicosis patients with no clinical symptoms of autoimmune diseases or malignant tumours, using ELISA for sFas. The serum sFas levels in the silicosis patients were significantly higher than those in healthy volunteers. Elevated serum sFas levels were also detected in patients with systemic lupus erythematosus but, unexpectedly, no difference was observed in sFas levels between progressive systemic sclerosis patients and healthy volunteers. On the other hand, there was no significant difference in the expression of Fas on peripheral blood lymphocytes between the patients with silicosis and age-matched healthy volunteers. These observations provided the first evidence that serum sFas levels are elevated in silicosis patients without clinical symptoms of autoimmune diseases or malignant tumours. It remains to be clarified whether patients with elevated sFas levels have a tendency to develop autoimmune diseases later, or whether some other distinct factor(s) is necessary to initiate the progression of autoimmune diseases.
Aged↗
Down regulation of protein kinase C during growth enhancement induced by interleukin-6 on a human myeloma cell line, KMS-11.
Interleukin-6 (IL-6) is one of the most important growth factors for myeloma cells. We examined the effect of recombinant IL-6 on the proliferation of five human myeloma cell lines, which were independently established AT Kawasaki Medical School. Only the KMS-11 cell line among these five lines showed growth enhancement induced by IL-6. Based on the results, a possible contribution of Ca(2+)-phospholipid-dependent protein kinase C (PKC) to the signal transduction in KMS-11 cells during growth enhancement was studied, since PKC may play an important role in malignant transformation or cell proliferation induced by some growth factors, such as IL-6. When exogenous IL-6 was added to KMS-11 culture, we observed (1) reduction of total PKC activity, and (2) translocation of PKC activity from its cytosol fraction to the membrane fraction. These findings may indicate that down regulation of PKC occurred during the myeloma cell proliferation induced by IL-6. However, IL-6 does not appear to be involved in cell proliferation and differentiation in the other cell lines studied.
Cell Division↗
Single-Mode Operations of a Circular Free-Electron Laser.
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Journal Article↗
bc1-1 rearrangement and cyclin D1 protein expression in multiple lymphomatous polyposis.
Multiple lymphomatous polyposis (MLP), characterized by multiple polyps involving long segments of the gastrointestinal (GI) tract, is believed to represent GI involvement by mantle cell lymphoma (MCL), primarily based on its histologic and immunophenotypic similarities with MCL. However, rearrangement of the bcl-1 locus, the molecular lesion characteristic of MCL, has not been investigated in this group of patients. The authors evaluated the morphologic, immunophenotypic, and molecular features of 18 cases of MLP and 8 B-cell lymphomas involving the GI tract (including 6 MALT lymphomas). All MLP cases presented with GI disease, and were histologically similar to MCL. DNA extracted from formalin-fixed, paraffin-embedded tissue was analyzed for evidence of bcl-1 rearrangement by PCR, using chromosome 11 specific and consensus JH primers. Amplifiable DNA was obtained in 24 of 26 cases (16 of 18 MLP cases and 8 of 8 controls). bcl-1 rearrangement was detected in 6 of 16 cases (38%), subsequently confirmed by sequencing of the breakpoint region, and in 0 of 8 controls. Immunostaining for cyclin D1 was positive in 14 of 18 MLPs, including the 6 bcl-1 rearranged cases and negative in 6 of 6 evaluable controls. The detection of bcl-1 rearrangement and cyclin D1 expression in cases of MLP supports the view that MLP represents primary MCL, of the GI tract. These techniques may also be helpful in differentiating MLP from other GI lymphomas, particularly low grade lymphomas of MALT, when only small routinely fixed endoscopic biopsies are available.
Adult↗
Epstein-Barr virus (EBV)-associated smooth-muscle tumor arising in a post-transplant patient treated successfully for two PT-EBV-associated large-cell lymphomas. Case report.
The association of Epstein-Barr virus (EBV) with smooth-muscle tumors was recently reported in the setting of acquired immunodeficiency syndrome (AIDS) and post-transplantation. We report a case of an EBV-associated smooth-muscle tumor arising in a post-transplant (PT) patient who previously was treated successfully for two EBV-associated PT large-cell lymphomas. A 4-year-old girl required cardiac transplantation for dilated cardiomyopathy when she was aged 23 months. Her PT regimen included cyclosporine, azothiaprine, and diltiazem. At 16 months PT, she presented with anemia, guaiac-positive stools, and an abdominal mass diagnosed as diffuse large-cell lymphoma of B-cell phenotype. Immunosuppressive therapy was reduced, and interferon and i.v. immunoglobulin were initiated. She rapidly developed signs of rejection, and a cardiac biopsy was performed, revealing grade IIIB rejection. Subsequently, immunosuppressive therapy increased. At 23 months PT, a biopsy was done of a large pelvic mass that was diagnosed as immunoblastic large-cell lymphoma. After treatment with chemotherapy and retinoic acid, the size of the mass markedly decreased. Follow-up computed tomography scan revealed multiple liver nodules. A needle biopsy of the liver showed a smooth-muscle tumor of indeterminate grade. Both the lymphomas and the smooth-muscle tumor contained EBV within > 95% of tumor cells by Epstein-Barr (EBER1) in situ hybridization, were of strain type A by Epstein-Barr nuclear antigen-2 (EBNA-2) polymerase chain reaction (PCR) and contained an identical 30 base-pair deletion (amino acids 346-355) of the latent membrane protein (LMP)-1 oncogene by PCR analysis. Notably, the initial large-cell lymphoma and the subsequent immunoblastic lymphoma each contained a unique p53 mutation, suggesting that they were distinct. These data suggest that the same virus contributed to the pathogenesis of both the malignant lymphomas and the smooth-muscle tumor.
Abdominal Neoplasms↗
Absence of p18 mutations or deletions in lymphoid malignancies.
p18 is a recently described cyclin-dependent kinase inhibitor (CDK-I) wih homology to p16 and p15. The latter two CDK-Is have been implicated as possible tumor suppressor genes in a wide variety of human tumors, including hematological malignancies. Because of p18's structural and functional homology to p16 and p15, we hypothesized that it may also function as a tumor suppressor gene in some lymphoid malignancies. To explore this possibility we examined 81 primary lymphoid tumors for deletion and mutation p18. The primary tumors included 40 T cell malignancies and 41 B cell malignancies. None of the lymphoid tumors studied possessed deletions of p18, including a group of lymphoblastic lymphomas which we previously reported to have deletions of p16 and p15. PCR-SSCP analysis of the p18 gene identified a single polymorphism of codon 114, but failed to demonstrate mutations in any of the lymphoid tumors. These results do not support a role for p18 in the pathogenesis of the lymphoid neoplasms studied.
Base Sequence↗
Detection of HHV-8/KSHV DNA sequences in AIDS-associated extranodal lymphoid malignancies.
Herpesvirus-like DNA sequences have been identified in a high proportion of both AIDS-associated and classical Kaposi's sarcoma, and in a small percentage of AIDS-associated malignant lymphomas. To determine the extent of involvement of this new agent designated HHV-8 (human herpesvirus type 8) or KSHV (Kaposi's sarcoma-associated herpesvirus) in human malignant lymphomas, we analyzed 24 AIDS-associated lymphoid malignancies and 100 non-AIDS-associated lymphomas by PCR and Southern blot analysis. Three of 24 lymphoid malignancies from patients with AIDS demonstrated HHV-8 sequences by Southern blot and PCR analyses. The fourth was positive by PCR only. None of the non-AIDS-associated lymphomas contained HHV-8 sequences. All three Southern blot positive samples were derived from extranodal regions, two from pleural effusions, and one from a soft tissue mass in the thigh. This latter patient initially presented with a pleural effusion. The fourth PCR positive but Southern blot negative tumor was from a gingival lymphoma in a patient with a history of Kaposi's sarcoma. All tumors positive for HHV-8 were also positive for EBV. These results confirm a recent report that this novel herpesvirus may play a role in AIDS-associated lymphomas especially in those with body cavity presentation.
Acquired Immunodeficiency Syndrome↗
[A study on the maternal plasma C21 steroids concentration during pregnancy].
During pregnancy, C21 steroids such as progesterone (P4), and cortisol (F), have been reported to be closely involved in uterine contraction. To clarify the association between changes in steroid hormones and the onset of delivery, we measured the concentrations of six C21 steroids in maternal blood by high performance liquid chromatography. Changes in each steroid hormone were evaluated by analysis of variance during pregnancy. Pregnenolone, a source of C21 steroids, gradually increased during pregnancy. P4 and 17P4, its metabolite, reached a peak 3 weeks before delivery and noticeably decreased thereafter. Accompanying a decrease in P4 and 17P4, 20P4 and F, its metabolite, were noticeably increased. The association among these steroid hormones was also evaluated. The correlation between P4 and F was reversed after 3 weeks before delivery. These results suggest that steroid hormones in the maternal blood begin to change dynamically about 3 weeks before delivery. In particular, a decrease in P4 and an increase in F seem to be closely related to the onset of delivery.
17-alpha-Hydroxyprogesterone↗
Analysis of the t(2;5)(p23;q35) translocation by reverse transcription-polymerase chain reaction in CD30+ anaplastic large-cell lymphomas, in other non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disease.
The t(2;5)(p23;q35) translocation is associated with a high percentage of anaplastic large-cell lymphomas (ALCL) of T- or null-cell phenotype. This translocation was recently cloned and results in the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to a novel tyrosine kinase-encoding gene designated anaplastic lymphoma kinase (ALK) on chromosome 2p23. Using a sensitive and specific reverse transcription-polymerase chain reaction (RT-PCR) assay to detect the NPM/ALK fusion transcript, we assessed the involvement of NPM/ALK in a series of histologically and immunohistochemically confirmed ALCL, in non-ALCL aggressive non-Hodgkin's lymphomas of T-cell phenotype, and in Hodgkin's disease (HD) to better define the morphologic spectrum of disease associated with this translocation. Twenty-four cases of ALCL were selected on the basis of CD30 positivity and histologic features. Seventeen cases presented as classical nodal and extranodal disease, four cases presented as primary cutaneous disease, and three were associated with human immunodeficiency virus (HIV) infection. As ALCL may show overlapping histology with both HD and other aggressive non-Hodgkin's lymphomas, particularly of T-cell phenotype (T-NHL), we also studied 34 cases of HD and 19 of T-NHL. NPM/ALK chimeric transcripts of identical size were detected in 11 of the 24 (46%) cases of ALCL. NPM/ALK fusion transcripts were found in 11 of 17 (65%) classical ALCL cases but were not detected in the four primary cutaneous cases of ALCL or in the three HIV-related ALCL cases. In addition, NPM/ALK transcripts were not detected in any of the 34 cases of HD or in the 19 cases of T-NHL. These data indicate that NPM/ALK fusion transcripts occur in a high percentage of classical nodal ALCL (65%). In addition, these data strongly suggest that ALCL, as defined in this study, is not pathogenetically related to either HD disease or the majority of other types of aggressive T-NHL. This is a US government work. There are no restrictions on its use.
Adolescent↗
Expression of mdr-1 in refractory lymphoma: quantitation by polymerase chain reaction and validation of the assay.
Measurement of P-glycoprotein and the gene that encodes it, mdr-1, is an important tool for assessing the impact of multidrug resistance in clinical cancer. We evaluated mdr-1 expression by a quantitative polymerase chain reaction (PCR) assay in 78 biopsy samples from 48 patients with refractory lymphoma enrolled on a trial of infusional chemotherapy (EPOCH) in which R-verapamil was added as an antagonist of P-glycoprotein in a subset of patients whose tumors were unresponsive to treatment. Expression of mdr-1 was detectable in all biopsies at the time of enrollment on study, and a fourfold or greater increase in mdr-1 expression was noted in 42% of patients at the time of treatment failure. Expression of mdr-1 was also detectable in biopsies from patients at the time of diagnosis of lymphoma. An endogenous control gene, beta 2-microglobulin, was quantitated for normalization of the mdr-1 values. The use of beta 2-microglobulin expression for normalization was validated in a subset of samples by comparing Northern blots detecting beta 2-microglobulin, beta actin, and GAPDH gene expression. Immunoblot analysis suggested that no major discrepancy was present between mRNA expression and protein level. Immunophenotyping of lymphomatous lymph nodes showed that infiltration of tumor cells ranged from 8% to 95% and of normal T cells from 1% to 83%. Expression of mdr-1 in normal T cells and monocytes was also shown to be low. The mdr-1 levels in patient samples were independent of T-cell contamination, suggesting that the presence of normal cells has at best a small impact on mdr-1 measurements. Expression of mdr-1 in lymphoma can be quantitated by PCR, and wide variations in expression can be observed. Increased expression in patients with refractory disease supports an important role for Pgp in drug resistance in lymphoma. These studies will aid in the design and interpretation of clinical trials in lymphoma.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Analysis of LAZ3 (BCL-6) status in B-cell non-Hodgkin's lymphomas: results of rearrangement and gene expression studies and a mutational analysis of coding region sequences.
The LAZ3 gene encodes a novel zinc-finger protein that shares homology with several Drosophila transcription factors. This gene was identified by its disruption in translocations involving chromosome 3q27 in diffuse large-cell lymphomas. To assess the frequency and role of this gene's involvement in lymphomagenesis and tumor progression, we examined a series of 170 cases of non-Hodgkin's lymphomas of B-cell lineage for LAZ3 gene rearrangement, expression, and mutation. The cases included 35 de novo diffuse aggressive lymphomas (DAL; 19 large-cell, 4 mixed-cell, and 12 large-cell immunoblastic), 52 transformed aggressive lymphomas derived from follicular lymphomas (TFL), 42 indolent follicular lymphomas (FL), 14 mantle cell lymphomas (MCL), and 27 small noncleaved cell lymphomas (SNCL). LAZ3 rearrangements were found in 10 DAL (28.6%), 9 TFL (17.3%), and 6 FL (14.3%), but not in any of the SNCL or MCL. LAZ3 rearrangement was not exclusive of bcl-2 rearrangement. Most rearrangement breakpoints mapped to a 10-kb BamHI-Xba I fragment located 5' to the LAZ3 coding sequence, consistent with previously reported breakpoint locations. Northern analysis of both rearranged and nonrearranged B-cell lymphoma cases showed similar levels of a transcript of approximately 3.8 kb, indicating that LAZ3 is broadly expressed in B-cell tumors and is not confined to rearranged cases. To investigate whether mutation of the LAZ3 gene might contribute to a potential role for this gene in lymphomagenesis, we screened the coding sequences of 13 rearranged cases, 6 nonrearranged cases, and 13 hematopoietic tumor cell lines. Although three probable polymorphisms were identified, mutations were detected in only 2 rearranged cases. Only 1 of these resulted in an amino acid substitution. Two cell lines (SU-DHL4 and Molt-4) also contained mutations; only one resulted in an amino acid substitution. We conclude (1) that LAZ3 rearrangements occur in a significant fraction of de novo DAL as well as in a smaller subset of indolent and transformed follicular lymphomas; (2) that LAZ3 message is expressed in both rearranged and nonrearranged B-cell lymphomas; and (3) that mutation of the LAZ3 gene does not contribute to its putative oncogenic role in most 3q27 translocated B-cell lymphomas.
Base Sequence↗
Involvement of CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 in human leukemias and lymphomas.
CDKN2 (p16INK4A/MTS1) and p15INK4B/MTS2 have been shown recently to be potent inhibitors of the cyclin D/cyclin-dependent kinase 4 complex. Both genes are candidates for the putative tumor suppressor gene located at chromosome 9p21. We examined a series of 14 hematopoietic cell lines and 117 primary lymphoid tumors for deletion and mutation of these genes. The primary tumors included 65 T-cell malignancies and 52 B-cell malignancies. The cell line study revealed 4 of 4 T-ALL lines to have homozygous deletions of CDKN2. Two of the 4 lines also showed homozygous deletions of MTS2, while the remaining 2 lines retained both MTS2 alleles. In the primary tumors, homozygous deletions of both CDKN2 and MTS2 were found in 35% of the T-ALL/lymphoblastic lymphoma (8 of 23). Homozygous deletions of both genes also occurred in 1 of 3 precursor B-ALLs. PCR-single strand conformational polymorphism analysis of CDKN2 exons 2 and 3 and MTS2 exon 2 failed to demonstrate mutations in either CDKN2 or MTS2 in any of the T- or B-cell malignancies, with two possible exceptions. These results are consistent with a role for CDKN2 and/or MTS2 in the pathogenesis of some lymphoid leukemia/lymphomas, particularly in T-ALL/lymphoblastic lymphoma.
Base Sequence↗