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PubMed1997

Properties of intraepithelial neoplasia relevant to the development of cancer chemopreventive agents.

Cancer chemoprevention is concerned with the development of drugs or diet supplements that will avert the onset or stop the progression of the intraepithelial neoplasia which precedes invasive cancer. Two basic processes underlie the onset and development of intraepithelial neoplasia. First is genomic instability (often associated with chronic diffuse epithelial hyperplasia), which is the increased production of genomic structural variants due to unrepaired DNA breaks with secondary formation of abnormal structures, including "mutator" mutations in genes responsible for genomic stability, gene copy amplification or loss from DNA breakage-fusion-anaphase bridge cycles, unequal sister chromatid exchange, and accumulation of double minutes. Second is the development within an epithelium having genomic instability of multicentric neoplastic lesions that independently progress through each of the following processes at a continuously accelerating rate: clonal evolution, hyperproliferation, production of genomic structural variants, and apoptosis. Recommended chemoprevention strategies based on these mechanisms are (1) early diagnosis and treatment of genomic instability before the appearance of intraepithelial neoplasia, i.e., during the "predysplastic" or "premorphologic" phase, (2) development of multiple agents that block intralesional proliferation at steps along the "command" pathways of mitotic signal transduction and along the "execute" pathways of synthesis of daughter cell components, (3) development of nontoxic antiinflammatory agents, antioxidants, antimutagens, and proapoptotics, (4) avoidance of "clonal escape" through use of drug combinations, and (5) use of computer-assisted quantitative image analysis to assay modulation of surrogate endpoints in chemoprevention clinical trials.

Carcinoma in Situ↗
PubMed2026

Grade progression and high-grade transformation in neuroendocrine neoplasms.

Epithelial neuroendocrine neoplasms (NENs) comprise a biologically diverse group of malignancies that span a wide spectrum of differentiation, proliferative activity, and clinical behavior. Contemporary classifications distinguish well-differentiated neuroendocrine tumors (NETs) from poorly differentiated neuroendocrine carcinomas (NECs). However, growing longitudinal data indicate that a subset of NETs may undergo temporal evolution characterized by rising Ki-67, increasing morphologic atypia, and acquisition of genomic alterations classically associated with NEC, particularly TP53 and, less commonly, RB1 inactivation. These phenomena, referred to as grade progression and high-grade transformation, can result in tumors with NEC-like behavior despite retention of a NET molecular backbone, creating diagnostic and therapeutic ambiguity. In this review, we synthesize recent evidence on the molecular, morphologic, and clinical features of gastroenteropancreatic NET grade progression and transformation, highlight the role of clonal evolution and treatment-associated selection pressure, and discuss implications for imaging, biopsy strategy, molecular profiling, and therapy selection.

Humans↗
PubMed1981

Heterogeneous blast cell crises in Philadelphia negative chronic granulocytic leukaemia.

A case of Philadelphia negative chronic granulocytic leukaemia (Ph1-CGL) is described showing features only previously demonstrated in Ph1+ disease. These features include: (1) lymphoid blast crisis, determined by morphology and immunological marker analysis; (2) dual blast cell populations that can be distinguished both morphologically and by immunological markers; (3) clonal evolution, as shown by the emergence of chromosome markers and in one of the cell lines a change in membrane phenotype. These changes were apparently associated with the emergence of a relatively drug resistant subclone of leukaemic cells. This study demonstrates that the lymphoid blast crisis of CGL, and its sequelae, can occur in Ph1- cases. It is similar in respect to morphology, enzyme, and membrane markers and responsiveness to vincristine and prednisolone therapy to the lymphoid blast crisis seen in Ph1+ CGL. This suggests that the Philadelphia chromosome is a clonal marker only, and its presence is not directly related to the subsequent clinical course of the disease.

Bone Marrow↗
PubMed1993

The cytogenetic scenario of chronic myeloid leukemia.

The Philadelphia chromosome (Ph), i.e., the reciprocal translocation t(9;22)(q34;q11), is found with great specificity in bone marrow cells from patients with chronic myeloid leukemia (CML). Variant Ph-producing translocations, seen in 5-10% of all patients, are all complex and involve the same molecular rearrangement as the regular t(9;22). Patients with classic and variant Ph-producing translocations are clinically and hematologically identical, and as a group differ from Ph-negative CML patients. In all patient groups, the occurrence of additional chromosome changes is an ominous sign indicating that disease progression is imminent. The chromosome changes occurring in excess of the Ph in CML are clearly nonrandom and two pathways of cytogenetic evolution may be distinguished. Major route changes comprise trisomy 8, i(17q), trisomy 19, and an extra Ph; totally, 71% of Ph-positive CML patients have at least one of these four major route changes. Six minor route changes, including five numerical abnormalities (-7, -17, +17, +21, and -Y) but also one structural aberration, t(3;21) (q26;q22), have been identified. At least one of these changes is found in 15% of all Ph-positive CML cases. Altogether, the four major route aberrations and the six minor route changes are present as part of the clonal evolution in 86% of CML with cytogenetic abnormalities in addition to the Ph chromosome.

Blast Crisis↗
PubMed1982

Evolution of Sézary syndrome in the course of hairy cell leukemia.

A patient with a history of "leukemia" for 19 yr and documented hairy cell (HC) leukemia for 10 yr developed mycosis fungoides and the Sézary syndrome. The manifestations of both diseases were diagnostic on clinical and pathologic grounds. Ultrastructural, immunohistochemical, and surface marker techniques proved the HC to have phenotypic characteristics of the T-helper subset of lymphocytes to which the Sézary cells (SC) also belonged. Both types of cells contained tartrate-resistant acid phosphatase. HC did not infiltrate the skin. SC did not contain ribosome lamellar complexes. Because of otherwise overlapping morphology and the apparent replacement of HC by SC, it is likely that the Sézary cells constituted a genetic variant of the original neoplastic clone represented by the hairy cells. Since the biologic and therapeutic implications of such clonal evolution may be important, subtle phenotypic changes should be looked for repeatedly in patients with these diseases.

Aged↗
PubMed1992

Morphology in patients with severe aplastic anemia treated with antilymphocyte globulin.

One hundred and seventeen patients with severe aplastic anemia (SAA) were treated at our institution between 1976 and 1990 with antilymphocyte globulin (ALG) therapy. Seventy-nine (68%) are alive and probability of survival at 14 years, according to Kaplan and Meier, is 62% +/- 12%. Twenty-six patients developed a late clonal complication: 11 had a myelodysplastic syndrome (MDS) and 17 had paroxysmal nocturnal hemoglobinuria (PNH); two patients had both. The cumulative risk at 10 years is 42%. The development of MDS/PNH after SAA directly affects survival. The probability of being alive at 14 years is 81% +/- 10% for patients with stable disease and 36% +/- 13% for those with clonal evolution (P = .001). To look for predictive signs, we reevaluated peripheral blood and bone marrow cytomorphology at presentation, during regeneration, and in remission. We examined the peripheral blood values for hemoglobin, reticulocytes, granulocytes, thrombocytes, mean corpuscular volume (MCV), and fetal hemoglobin, as well as bone marrow for cellularity, erythropoiesis, myelopoiesis, and megakaryopoiesis. ALG therapy induces slow and incomplete recovery. Although in "remission," ALG patients have lower hemoglobin values, higher reticulocyte counts, lower granulocyte and platelet values, and a higher MCV and fetal hemoglobin than normal controls. They retain a reduced number of megakaryocytes and a persistence of atypical monocytes in bone marrow morphology as stigmata of their disease. Patients with late clonal complications show distinct morphologic abnormalities: patients with PNH have higher MCVs, higher granulocyte and reticulocyte counts, and more dyserythropoiesis at diagnosis and a lower hemoglobin with an increased proportion of erythroblasts in the bone marrow in "remission." Patients who later developed MDS are not different from the total patient population at diagnosis. After therapy, these patients are characterized by the presence of ring sideroblasts and atypical monocytes during regeneration and by a persistent increase in MCV, a higher fetal hemoglobin, lower granulocyte values, and megakaryocytic dysplasia during "remission." Thus, routine morphologic follow-up examination of blood and bone marrow can discover patients at risk for late hematologic complications after ALG therapy.

Adult↗
PubMed1993

Overrepresentation of chromosome 12p sequences and karyotypic evolution in i(12p)-negative testicular germ-cell tumors revealed by fluorescence in situ hybridization.

Human testicular germ-cell tumors (TGCTs) comprise a heterogeneous group of solid neoplasms. These tumors are characterized by the presence of a highly specific chromosomal abnormality, i.e., an isochromosome of the short arm of chromosome 12. At present, this i(12p) chromosome is found in more than 80% of TGCTs. Isochromosome 12p has also been observed in some ovarian and extragonadal germ cell tumors. In the remaining so-called i(12p)-negative TGCTs other abnormalities involving chromosome 12, mainly 12p, can be found. In order to establish whether 12p abnormalities other than i(12p) are a common phenomenon in TGCTs, a panel of 11 i(12p)-negative tumors was investigated using multicolor fluorescence in situ hybridization. All TGCTs examined appeared to contain chromosomal abnormalities involving 12p, resulting in a distinct overrepresentation of short arm sequences. In addition, indications were obtained for a clonal evolution in one of the tumors. Our data suggest that the occurrence of 12p abnormalities is a common phenomenon in i(12p)-negative TGCTs and that these abnormalities, analogous to i(12p), may contribute to the process of tumor development.

Chromosome Aberrations↗
PubMed1990

Evolving abundance and clonal pattern of human germinal center B cells during childhood.

Childhood is a critical period for the development of the memory B-lymphocyte repertoire necessary in protective humoral immunity. This study addressed the natural history of memory B cells based on the previous identification of germinal center and mantle zone cells as the probable precursor and mature memory cell populations, respectively. Using flow cytometric quantitation of these B-cell subpopulations in human tonsil, we found that germinal center cells were abundant (70% of tonsil B cells) during early childhood (2 to 3 years), but decline by early adolescence (8 to 14 years) to a low level (33%, P = .0003). To study the clonal evolution of these B-cell subpopulations, germinal center and mantle zone B cells were isolated using a preparative magnetic immunobead method, and analyzed using a novel polymerase chain reaction-based quantitative assay to measure the abundance of B-cell clones bearing certain rearranged VH subfamilies. Two VH subfamilies were informative: VH1N clones were uniquely deficient in germinal center B cells at the early age period, but became abundant in later childhood; and VH3L clones were absent among germinal center cells regardless of age. In contrast, B-cell clones bearing each VH subfamily were abundant in the mantle zone subpopulation throughout childhood. These findings suggest that the abundance and clonal pattern of germinal center B cells evolves during childhood, presumably due to changing antigenic or ontogenic processes. Moreover, the distinct clonal pattern of germinal center versus mantle zone B cells suggests that a major phase of clonal selection occurs after germinal center emigration.

Adolescent↗
PubMed1992

Cytogenetic analysis in the diagnosis of acute leukemia.

Acute leukemias are characterized by acquired genetic rearrangements that, in most cases, can be detected by cytogenetic methods as clonal chromosomal abnormalities. Whereas primary abnormalities contribute to the establishment of the leukemia and often are seen as solitary changes, secondary aberrations accrue during clonal evolution. Both abnormalities are nonrandom in distribution. The pattern differs between acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) and from subtype to subtype. Some abnormalities are so characteristic as to be virtually pathognomonic for particular types of leukemia. The importance of cytogenetic characterization of leukemias is thus two-fold. First, the recurrent aberrations provide insight into the pathogenetic mechanisms that are operative. They pinpoint areas of the human genome that carry genes or regulatory sequences whose function is disrupted in neoplastic cells. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have direct clinical importance. The finding of an acquired clonal chromosomal abnormality in hematopoietic cells identifies the presence of a neoplastic disease. The aberration profile may reveal whether the patient has ALL or ANLL and which subtype it is. Remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern is an independent prognostic parameter that should be considered when the choice of therapy is made.

Chromosome Aberrations↗
PubMed1990

Chromosome analysis of 31 Wilms' tumors.

Cytogenetic analysis was done on 31 Wilms' tumors, including 2 renal tumors of clear cell sarcoma type, using short term cultures of primary tumors and/or nude mouse passages. Nonrandom secondary chromosome abnormalities, in particular, were noted as evidence of clonal evolution. Apparently normal karyotypes were found in 5 Wilms' tumors, all in patients less than or equal to 22 months old, and in one clear cell sarcoma. Abnormal karyotypes were seen in 25 tumors (80%); 6 were pseudodiploid, 3 were hypodiploid, and 16 (52%) were hyperdiploid, of which 8 had a modal number of 47-49 and 8 had a modal number of 50-55. Nonrandom structural abnormalities involved 1p/1q, 11p, 7p/7q, 16p/16q, 12q, and 17p/17q. Nonrandom numerical abnormalities included +6, +8, and +18. Trisomy 12 was the most common abnormality, structural or numerical, seen in 52% of tumors (81% of the hyperdiploid). In 2 tumors the +12 was the only apparent abnormality; in 1 other tumor an i(12q) was seen, suggesting that +12 may have special significance in the clonal progression of Wilms' tumor. Informative karyotypes of 68 Wilms' tumors from other reports were reviewed and compared to results in this series.

Child↗
PubMedDate not supplied

The rat Nb2 lymphoma: a novel model for tumor progression.

Tumor progression of cancers is manifested by phenotypic property changes including development of hormone/growth factor independence and metastatic ability. The progression results from acquired genomic alterations leading to clonal heterogeneity and outgrowth of more aggressive and therapy-resistant sublines. Previously, a cultured rat "Nb2 lymphoma" cell line was established, whose viability depends critically on the hormone, prolactin, acting as the principal growth factor. By prolactin starvation, prolactin-independent sublines were generated which possessed the parent karyotype plus extra acquired chromosomal changes (clonal evolution). In this study, the parent line (Nb2-U17) and a cloned subline (SFJCD1) were compared for metastatic ability using single s.c. tumor transplants in Noble rats. Rats (22) bearing Nb2-U17 tumors showed no evidence of metastases at autopsy, even when tumors at implantation site reached a size of 9 cm (length + width). In contrast, rats (19) bearing SFJCD1 tumors showed multiple metastases (liver, kidney) when transplants exceeded 5 cm. This difference in metastatic ability may be related to the acquisition of an inversion in chromosome 1, i.e. inv(1)(q31q41). The 1q41 locus is adjacent to the reported H-ras-1 proto-oncogene locus (1q41-q42). In another subline, tetraploidization (flow cytometric analysis, karyotyping) occurred spontaneously following prolonged culturing (20 mo). Together, the parent Nb2 lymphoma line and its clonal derivatives provide a novel system for studying cellular and molecular mechanisms underlying tumor progression to the metastatic phenotype.

Animals↗
PubMed1996

Towards a unified evolutionary genetics of microorganisms.

I propose here that evolutionary genetics, apart from improving our basic knowledge of the taxonomy and evolution of microbes (either eukaryotes or prokaryotes), can also greatly contribute to applied research in microbiology. Evolutionary genetics provides convenient guidelines for better interpreting genetic and molecular data dealing with microorganisms. The three main potential applications of evolutionary genetics in microbiology are (a) epidemiological follow-up (with the necessity of evaluating the stability of microbial genotypes over space and time); (b) taxonomy in the broad sense (better definition and sharper delimitation of presently described taxa, research of hidden genetic subdivisions); and (c) evaluation of the impact of the genetic diversity of microbes on their relevant properties (pathogenicity, resistance to drugs, etc). At present, two main kinds of population structure can be distinguished in natural microbial populations: (a) species that are not subdivided into discrete phylogenetic lineages (panmictic species or basically sexual species with occasional bouts of short-term clonality fall into this category); (b) species that are strongly subdivided by either cryptic speciation or clonal evolution. Improvements in available statistical methods are required to refine these distinctions and to better quantify the actual impact of gene exchange in natural microbial populations. Moreover, a codified selection of markers with appropriate molecular clocks (in other words: adapted levels of resolution) is sorely needed to answer distinct questions that address different scales of time and space: experimental, epidemic, and evolutionary. The problems raised by natural genetic diversity are very similar for all microbial species, in terms of both basic and applied science. Despite this fact, a regrettable compartmentalization among specialists has hampered progress in this field. I propose a synthetic approach, relying on the statistical improvements and technical standardizations called for above, to settle a unified evolutionary genetics of microorganisms, valid whatever the species studied, whether eukaryotic (parasitic protozoa and fungi) or prokaryotic (bacteria). Apart from benefits for basic evolutionary research, the anticipated payoff from this synthetic approach is to render routine and common-place the use of microbial evolutionary genetics in the fields of epidemiology, medicine, and agronomy.

Animals↗
PubMed1995

Frequent ongoing T-cell receptor rearrangements in childhood B-precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease.

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.

Base Sequence↗
PubMed1990

Cytogenetics in the investigation of haematological disorders.

Chronic and acute, myeloid and lymphatic haematological neoplasms are characterized by acquired genetic rearrangements that, in the majority of cases, can be detected as clonal chromosomal abnormalities. The aberrations are either primary, meaning that they contribute to the establishment of the neoplasm, or secondary, in which case they are acquired during the clonal evolution and malignization of the neoplastic cells. The abnormalities are non-randomly distributed; the aberration pattern differs from disease to disease and sometimes is so characteristic that individual rearrangements may be virtually pathognomonic for particular neoplasms. The cytogenetic characterization of haematological malignancies is of two-fold importance. First, the recurrent aberrations provide us with an insight into the pathogenetic mechanisms that are operative. They pinpoint those areas of the human genome that carry genes or regulatory sequences whose function is disturbed in leukaemias and lymphomas. Using DNA recombinant techniques in addition to chromosome-level investigations of these cancer-associated rearrangements, the molecular pathology of leukaemias and lymphomas is now gradually being unravelled. Second, even before the long-term goal of a more fundamental understanding of the neoplastic process is reached, the cytogenetic aberrations have a direct clinical importance. The finding of an acquired, clonal chromosome abnormality in haematopoietic cells (-Y in old men is an exception) means that the patient has a neoplastic disease. Often, but by no means always, the type of aberration is also informative as to which type of neoplasm is present. During therapy, remission and relapse can be monitored by cytogenetic analyses. Finally, the karyotypic pattern influences prognosis and may thus be taken into account when the choice of therapy is made.

Chromosome Aberrations↗
PubMed1991

Evidence for clonal disease by magnetic resonance imaging in patients with hypoplastic marrow disorders.

Some patients with hypoplastic marrow disorders, including aplastic anemia (AA), are at risk for clonal evolution to myelodysplastic syndromes (MDS) and leukemia. Magnetic resonance imaging (MRI) of marrow of the spine, pelvis, and femurs was performed in 24 patients with hypoplastic marrow disorders. In 12 patients (three AA, nine MDS) MRI was compatible with the clinical and biopsy diagnoses and served to define the spectrum of marrow patterns in these disorders. In eight patients with hypocellular marrow biopsies and a clinical diagnosis of AA, MRI showed an unexpected inhomogeneous or diffuse cellular pattern. Concurrent or subsequent marrow or cytogenetic studies have led to diagnoses of hypoplastic MDS in seven of these patients. In four patients with prolonged hypoplasia after bone marrow transplantation for lymphoma, a speckled pattern superimposed on a fatty background appeared in serial MRI studies. One case evolved to AML, two developed megaloblastic foci, and one remains hypoplastic at 19 months. This study suggests that MRI is able to detect early clonal disease in patients with AA, and can distinguish AA from hypoplastic MDS.

Adult↗
PubMed2001

Trypanosoma cruzi: presence of the two major phylogenetic lineages and of several lesser discrete typing units (DTUs) in Chile and Paraguay.

Multilocus enzyme electrophoresis (MLEE) of 99 Chilean and 11 Paraguayan stocks of Trypanosoma cruzi, the agent of Chagas disease, was performed for 22 variable genetic loci. As previously shown for this parasite in other geographic areas, a pattern of long-term clonal evolution of T. cruzi genotypes was inferred, both by strong departures of Hardy-Weinberg expectations and high linkage disequilibrium. The presence of the two major phylogenetic lineages that subdivide the species T. cruzi [Tibayrenc, M., 1995. Population genetics of parasitic protozoa and other microorganisms. In: Baker, J.R., Muller, R., Rollinson, D. (Eds.), Advances in Parasitology, vol. 36, Academic Press, New York, pp. 47-115; Souto, R.P., Fernandes, O., Macedo, A.M., Campbell, D.A., Zingales, B., 1996. DNA markers define two major phylogenetic lineages of Trypanosoma cruzi. Mol. Biochem. Parasitol. 83, 141-152], and of several lesser genetic subdivisions ('discrete typing units' or DTUs; Tibayrenc, M., 1998a. Genetic epidemiology of parasitic protozoa and other infectious agents: the need for an integrated approach. Int. J. Parasitol. 28 (1), 85-104; Tibayrenc, M., 1998b. Beyond strain typing and molecular epidemiology: integrated genetic epidemiology of infectious diseases. Parasitol. Today 14, 323-329; Tibayrenc, M., 1998c. Integrated genetic epidemiology of infectious diseases: the Chagas model. Mem. Inst. Oswaldo Cruz 93 (5), 577-580), was recorded in this region. Comparison between clonal populations in sylvatic and domestic transmission cycles of the disease in Chile strongly suggests that these two cycles are at least partially separated from one another.

Animals↗
PubMed1980

Evolution of cultured leukemic cell lines monitored by chromosomal and immunologic analysis.

We have investigated the karyotypes and markers of B lymphocyte differentiation in two leukemic cell lines, NALM-6-B and NALM-6-MI, both derived from a patient with non-T, non-B acute lymphoblastic leukemia. Both possess characteristics of thymus-independent, bursal-equivalent (B) lymphocytes. By means of immuno-fluorescence techniques, NALM-6-B was shown to possess 47% surface membrane immunoglobulin-positive (Slg+) cells, while NALM-6-MI is surface membrane immunoglobulin-negative (Slg-), but does possess cytoplasmic immunoglobulin M (ClgM+) in more than 90% of the cells. The Slg- ClgM+ phenotype, coupled with morphologic features, is consistent with NALM-6-MI being arrested at a stage early in B-lymphocyte differentiation (a "pre-B" cell). The predominant banded chromosome karyotype of NALM-6-B is pseudodiploid with a translocation of chromosomal material from the long arm of a chromosome 5 to the short arm of a chromosome 12 (5q-/12p+) and a marker Y chromosome. NALM-6-MI possesses the same marker Y chromosome and a deletion of the long arm of chromosome 5(5q-) since in most cells material missing from chromosome 5 does not appear on the short arm of chromosome 12. Within the limits of resolution available with the banding technique, no other karyotypic differences are observed in the two cell lines. The history of the two cell lines, the karyotypic analysis, and the pattern of immunoglobulin markers indicate the possible clonal evolution of NALM-6-MI from NALM-6-B and implicate a portion of the long arm of chromosome 5 in lymphoid differentiation of these leukemic cell lines.

Adult↗
PubMed1995

Localized gastric non-Hodgkin's lymphoma of high-grade malignancy in patients with pre-existing chronic lymphocytic leukemia or immunocytoma.

Analyses for clonality in cases of Richter's syndrome have provided evidence for a clonal evolution of high-grade lymphoma in most patients, while in others an independent cellular clone seems to exist in the secondary neoplasm. Richter's syndrome with an isolated high-grade lymphoma of the stomach has been rarely reported in patients with pre-existing B cell chronic lymphocytic leukemia (CLL). We investigated four cases of CLL or lymphoplasmacytoid immunocytoma (LPIC) with development of a localized high-grade B cell lymphoma in the stomach. Southern blotting showed different rearrangements of the immunoglobulin light and heavy chain genes in the tumor cells of the low-grade lymphoma and the gastric tumor in two cases. Comparison of the DNA sequences of the CDR3 region of the immunoglobulin genes revealed different clones in another case. By means of chromosomal in situ hybridization, trisomy 3 was detected in two cases of high-grade lymphoma of the stomach, but not in the cells of the associated low-grade tumor. Our findings indicate that high-grade non-Hodgkin's lymphomas arising localized in the stomach of patients with CLL or immunocytoma are not clonally related to the pre-existing low-grade lymphoma and, therefore indeed, present true secondary neoplasms.

Aged↗