No abstract available.
Hand* ; Humans

Investigations of the anti-tumor activity of recombinant mouse TNF and etoposide(VP-16) in a nude mouse subcutaneous implantation xenograft model utilizing the CURC-1 human renal cell carcinoma cell line were performed. Recombinant mouse tumor necrosis factor-alpha(rTNF-alpha) and VP-16. both well known cytotoxic and cytostatic anticancer agents were evaluated singly and in combination against subcutaneously growing CURC-1. The results were as follows : 1. In the absence of treatment(Group I). subcutaneously growing CURC-1 tumor nodules demonstrated continued rapid growth. 2. Administration of rTNF(Group II) induced significant tumor regression in the subcutaneous nodules. 3. Administration of rTNF and Etoposide(Group III) demonstrated significant tumor growth inhibition. On histopathological findings, Group I (control) shows rare leukocyte infiltration and no tumor necrosis. In contrast, Group II shows tumor necrosis and more leukocyte infiltration than Group I . Group III demonstrates tumor necrosis. tumor cell degeneration and more leukocyte infiltration than Group II. These results suggest that TNF have antineoplastic effect against subcutaneous human renal cell carcinoma nodule but the synergistic effect of TNF with VP-l6 is uncertain.
Animals ; Antineoplastic Agents ; Carcinoma, Renal Cell* ; Cell Line ; Etoposide* ; Heterografts* ; Humans ; Leukocytes ; Mice ; Mice, Nude* ; Necrosis ; Robenidine ; Tumor Necrosis Factor-alpha*

A variant Philadelphia chromosome (Ph) is generated from translocation of one or more partner chromosomes in addition to chromosomes 9 and 22. We have described the cases of 2 patients bearing variant Ph detected by interphase FISH but not detected by G-banded karyotyping and metaphase FISH. FISH was performed using BCR/ABL dual color dual fusion translocation probes (Abbott Molecular, USA). A 52-year-old man was diagnosed with acute leukemia of mixed phenotype. G-banded karyotyping showed 46,XY,t(9;22)(q34;q11.2)[12]/47,idem,+der(22)t(9;22)[5]/46,XY[3]. Interphase FISH revealed nuc ish(ABL1,BCR)x3(ABL1 con BCRx2)[329/450]/(ABL1,BCR)x4(ABL1 con BCRx3)[5/450]/(AL1,BCR)x3(ABL1 con BCRx1)[44/450]. Metaphase FISH showed ish (9;22)(ABL1+,BCR1+;BCR+,ABL+)[22]/der(22)(BCR+,ABL1+)[3]. The other case was that of a 31-yr-old male patient diagnosed with CML in the blastic phase. G-banded karyotyping of all 20 metaphase cells showed 47,XYYc,dup(1)(q21q32),del(7)(p11.2),t(9;22)(q34;q11.2). Interphase FISH revealed nuc ish(ABL1,BCR)x3(ABL1 con BCRx2)[254/600]/(ABL1,BCR)x3(ABL1 con BCRx1)[191/600]. Metaphase FISH showed ish t(9;22)(ABL1+,BCR+;BCR+,ABL1+)[16]. These results suggest that typical t(9;22) and variant Ph may coexist in the same patient, and interphase FISH may facilitate the detection of the variant Ph that cannot be detected by G-banded karyotyping alone.
Adult ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 9 ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Interphase ; Karyotyping ; Leukemia/diagnosis/genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis/genetics ; Male ; Metaphase ; Middle Aged ; Phenotype ; *Philadelphia Chromosome ; Translocation, Genetic

Chromosomes forming a corresponding ring cannot be clearly defined by conventional cytogenetics or FISH. Karyotypic analyses using whole-genome single nucleotide polymorphism arrays (SNP-A) may result in the identification of previously cryptic lesions and allow for more precise definition of breakpoints. We describe a case of AML with metaphase cells bearing -5, del(11)(q22), and +r. With SNP-A, a 5p-terminal deletion (11 megabases [Mb]), a 5q-terminal deletion (27 Mb), an 11q-interstitial deletion (29 Mb), and a 21q gain (3 Mb) were identified. Therefore, the G-banded karyotype was revised as 46, XY, r(5)(p15. 2q33.2), del(11)(q14.1q23.2), dup(21)(q22.13q22.2)[18]/46,XY[2]. SNP-A could be a powerful tool for characterizing ring chromosomes in which the involved chromosomes or bands cannot be precisely identified by conventional cytogenetics or FISH.
Chromosome Deletion ; *Chromosomes, Human, Pair 5 ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Leukemia, Myeloid, Acute/*diagnosis/genetics ; Male ; Metaphase ; Middle Aged ; Oligonucleotide Array Sequence Analysis ; *Polymorphism, Single Nucleotide ; *Ring Chromosomes

A genomic instability called chromothripsis occurs as a single catastrophic event, generating massive complex genomic rearrangement with a possible characteristic pattern of copy number oscillations. Here, we report a case of secondary plasma cell leukaemia (PCL) showing chromothripsis identified by single nucleotide polymorphism array (SNP-A)-based karyotyping. A 53-year-old male patient was diagnosed as having secondary PCL four years after he was diagnosed with multiple myeloma, and he died four days later due to intracerebral haemorrhage. Chromosomal analysis and fluorescence in situ hybridization (FISH) revealed the deletions of 13q and 17p and an insertion of 1q. Further, genomic aberrations that were not detected by chromosomal analysis and FISH were identified by SNP-A. In particular, SNP-A revealed numerous alternating copy number state switches involving one, two, or three copy number states on chromosome 7q, suggesting the presence of chromothripsis. The present case suggests that chromothripsis may occur in secondary PCL and can be inferred from genomic copy number profiles identified by SNP-A.
Fluorescence ; Genomic Instability ; Humans ; In Situ Hybridization ; Karyotyping ; Male ; Middle Aged ; Multiple Myeloma ; Plasma Cells* ; Polymorphism, Single Nucleotide

Trisomy 22 is closely associated with inv(16) or t(16;16) and could be a marker of cryptic rearrangement of CBFB/MYH11 in acute myeloid leukemia (AML). Trisomy 22 not associated with CBFB/MYH11 rearrangement is a rare event. Here, we report a case diagnosed as refractory anemia with excess blasts-2 (RAEB-2) with sole trisomy 22 in the absence of CBFB/MYH11 rearrangement. The cytogenetic study of bone marrow cells disclosed trisomy 22 in 10% of metaphase cells analyzed. The other chromosomal abnormalities were not found. Fluorescence in situ hybridization (FISH) using CBFB/MYH11 probe to detect cryptic inv(16)(p13q22) showed negative result. We also excluded rearrangements of chromosome 5, 7, 8, 20, and ETV6 by FISH. Sole trisomy 22 not associated with inv(16) is a true entity.
Anemia, Refractory ; Bone Marrow Cells ; Chromosome Aberrations ; Chromosomes, Human, Pair 22 ; Chromosomes, Human, Pair 5 ; Cytogenetics ; Fluorescence ; In Situ Hybridization ; Leukemia, Myeloid, Acute ; Metaphase ; Myelodysplastic Syndromes ; Trisomy

Translocations leading to fusions between the immunoglobulin heavy chain gene (IGH) and various partner genes have been reported in B-cell precursor acute lymphoblastic leukemia (B-ALL). However, submicroscopic deletions within IGH in B-ALL have not been rigorously assessed. In this study, we investigated characteristics of IGH submicroscopic deletions, by FISH, in B-ALL with IGH rearrangements. FISH was performed by using commercially available IGH dual-color break-apart rearrangement probes (Abbott/Vysis, Downers Grove, IL, USA; Kreatech, Amsterdam, Netherlands). The study group included seven B-ALL patients with IGH rearrangements, observed by FISH. Among them, two exhibited deletion of the 5' variable region of IGH by FISH. The B-ALL in these two patients included two kinds of abnormal cells; one had an IGH rearrangement without any IGH submicroscopic deletion, while the other had an IGH submicroscopic deletion, which showed that one normal fusion signal and one 3' IGH signal were detected. Thus, submicroscopic deletion of the IGH 5' variable region may have occurred in either the native or rearranged chromosome 14. These findings indicate that B-ALL with IGH rearrangements may be accompanied by submicroscopic deletions of the IGH 5' variable region, which can be detected by FISH. The clinical significance of such deletions is unclear, but the loss of part of the IGH gene in B-ALL warrants further study.
Adult ; Child ; Female ; *Gene Deletion ; *Gene Rearrangement ; Humans ; Immunoglobulin Heavy Chains/*genetics ; In Situ Hybridization, Fluorescence ; Infant ; Male ; Middle Aged ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/*genetics/pathology ; Young Adult

Prognosis is known to be better in cases with isolated chromosomal abnormalities than in those with complex karyotypes. Accordingly, del(20q) as an isolated abnormality must be distinguished from cases in which it is associated with other chromosomal rearrangements for a better stratification of prognosis. We report a case of an isolated del(20q) abnormality with additional genomic aberrations identified using whole-genome single nucleotide polymorphism array (SNP-A)-based karyotyping. A 39-yr-old man was diagnosed with AML without maturation. Metaphase cytogenetic analysis (MC) revealed del(20)(q11.2) as the isolated abnormality in 100% of metaphase cells analyzed, and FISH analysis using D20S108 confirmed the 20q deletion in 99% of interphase cells. Using FISH, other rearrangements such as BCR/ABL1, RUNX1/RUNX1T1, PML/RARA, CBFB/MYH11, and MLL were found to be negative. SNP-A identified an additional copy neutral loss of heterozygosity (CN-LOH) in the 11q13.1-q25 region. Furthermore, SNP-A allowed for a more precise definition of the breakpoints of the 20q deletion (20q11.22-q13.31). Unexpectedly, the terminal regions showed gain on chromosome 20q. The patient did not achieve complete remission; 8 months later, he died from complications of leukemic cell infiltrations into the central nervous system. This study suggests that a presumably isolated chromosomal abnormality by MC may have additional genomic aberrations, including CN-LOH, which could be associated with a poor prognosis. SNP-A-based karyotyping may be helpful for distinguishing true isolated cases from cases in combination with additional genomic aberrations not detected by MC.

Cases of clonal cytogenetic abnormalities in Philadelphia-negative cells during the treatment of Philadelphia-positive CML have been previously reported. However, clonal abnormalities unrelated to the original t(8;21) or t(15;17) karyotype are not common. Deletion of 20q (del(20q)) is one of the most common recurrent cytogenetic abnormalities in myeloid neoplasms. Here we describe 3 patients with t(8;21), t(15;17), or t(9;22) who developed unrelated del(20q) after successful treatment of leukemia. We retrospectively reviewed the cytogenetic results of 23 AML patients with t(8;21)(q22;q22), 28 AML patients with t(15;17)(q22;q12), and 47 CML patients with t(9;22)(q34;q11.2). We identified 3 patients with del(20q) as the only clonal aberration unrelated to the primary karyotype when they achieved complete morphologic and cytogenetic remission. The latency period between diagnosis and emergence of del(20q) was 1, 114, and 35 months for the 3 patients, respectively. There was no evidence of therapy-related MDS/AML during the follow-up period. In 1 AML patient with t(8;21), relapse occurred in a t(8;21)(q22;q22) clone and the del(20q) clones were lost. The clinical significance of del(20q) as an unrelated clonal aberration is unknown, but our study suggests that del(20q) does not cause therapy-related MDS/AML or indicate disease progression.
Chromosome Aberrations ; Chromosome Deletion ; Chromosomes, Human, Pair 20 ; Clone Cells ; Cytogenetics ; Disease Progression ; Follow-Up Studies ; Humans ; Karyotype ; Latency Period (Psychology) ; Leukemia ; Recurrence ; Retrospective Studies

Chronic lymphocytic leukemia (CLL) and multiple myeloma (MM) are both lymphoproliferative disease occurring in different stages of B cell oncogeny. An increased incidence of secondary malignancies in patients with CLL is well recognized, however, the coexistence of both disorders in the same patient was very rare. Furthermore, clonal relationship between these diseases has not been clearly established. We report the occurrence of MM during the course of CLL. A 68-year-old patient was presented with general weakness and bone marrow aspiration showed a hypercellular marrow with 80% mature lymphocytes. At 5 months after diagnosis of CLL, bone marrow of the patient showed increased immature plasma cells. Serum protein electrophoresis showed monoclonal gammopathy and serum immunoelectrophoresis IgG kappa type monoclonality. The patient received six cycles of VAD (vincristine, adriamycin, dexamethasone) chemotherapy, but died of pneumonia and sepsis.
Aged ; Bone Marrow ; Diagnosis ; Doxorubicin ; Drug Therapy ; Electrophoresis ; Humans ; Immunoelectrophoresis ; Immunoglobulin G ; Incidence ; Leukemia, Lymphocytic, Chronic, B-Cell* ; Lymphocytes ; Multiple Myeloma* ; Paraproteinemias ; Plasma Cells ; Pneumonia ; Sepsis