Search PubMed⌕ Search

Biomedical subjects

C A Felix

Publications and source records attributed to C A Felix.

51 records · Page 3Linked to original sources
PubMed1993

Common region of ALL-1 gene disrupted in epipodophyllotoxin-related secondary acute myeloid leukemia.

Translocations at chromosomal band 11q23 characterize most de novo acute lymphoblastic leukemias (ALL) of infants, acute myeloid leukemias (AML) of infants and young children, and secondary AMLs following epipodophyllotoxin exposure. The chromosomal breakpoints at 11q23 have been cloned from isolated cases of de novo ALL and AML. Using an 859-base pair BamHI fragment of human ALL-1 complementary DNA that recognizes the genomic breakpoint region for de novo ALL and AML, we investigated two cases of secondary AML that followed etoposide-treated primary B-lineage ALL. In the first case, the translocation occurred between chromosomes 9 and 11 and the breakpoint at 11q23 localized to the same 9-kilobase region of the ALL-1 gene that is disrupted in most of the de novo leukemias. In the second case the translocation was between chromosomes 11 and 19. The breakpoint occurred outside of the ALL-1 breakpoint cluster region.

Child, Preschool↗
PubMed1993

Identification of an altered immunoglobulin heavy-chain gene rearrangement in the central nervous system in B-precursor acute lymphoblastic leukemia.

In B-precursor acute lymphoblastic leukemia (ALL), the nucleotide sequence of the complementarity determining region III (CDRIII) in the rearranged immunoglobulin heavy chain gene (IgH) has been used as a molecular fingerprint to identify the leukemic cells. In a child with B-precursor ALL without central nervous system (CNS) disease at diagnosis and a subsequent isolated CNS relapse, we examined the stability of the rearranged IgH by comparing the nucleotide sequences of the CDRIII in the leukemic cells from the marrow at diagnosis to the sequences in the leukemic cells from the cerebrospinal fluid at relapse. Whereas two of the three IgH sequences isolated from the leukemic cells at CNS relapse were identical to sequences originally isolated from the marrow lymphoblasts at diagnosis, the third CNS sequence was similar but not identical to the third marrow sequence. The third IgH sequence identified in the CNS differed from the marrow sequence only at the variable gene segment adjoining the CDRIII. Using a detection method based on the polymerase chain reaction, the altered IgH sequence identified in the leukemic cells from the cerebrospinal fluid was noted to be present in the CNS at a higher frequency than the related diagnostic sequence and was not detected in the marrow either at diagnosis or at CNS relapse. These findings indicate that the clonal pattern of leukemia in the CNS may differ from that in the marrow.

Base Sequence↗
PubMed1993

Sequential development of Wilms tumor, T-cell acute lymphoblastic leukemia, medulloblastoma and myeloid leukemia in a child with type 1 neurofibromatosis: a clinical and cytogenetic case report.

In her 8 1/2 years of life, a girl with neurofibromatosis type 1 (NF1) developed four sequential primary malignant neoplasms: Wilms tumor, T-cell acute lymphoblastic leukemia, medulloblastoma and acute myeloid leukemia. The last three tumors were characterized by chromosomal abnormalities non-randomly associated with that particular disease. There was no evidence of germline p53 mutation or of mutation of p53 in the last two tumors. We hypothesize that an unusual mutation of the NF1 gene in this child promoted growth in tissues where the normal or mutated NF-1 gene product is usually silent or growth inhibitory.

Bone Marrow↗
PubMed1993

A novel germline p53 splicing mutation in a pediatric patient with a second malignant neoplasm.

A novel germline p53 splicing mutation was identified in a pediatric patient with two metachronous primary cancers that are constituent tumors of the Li-Fraumeni syndrome. Genomic DNA from the second tumor showed the same mutation and loss of heterozygosity at the p53 locus. The mutant mRNA and protein were present in the tumor tissue. In contrast, in the normal tissues bearing the germline mutation in the heterozygous state, predominantly normal mRNA was expressed and the mutant p53 protein was not detectable. The functional silence and relative lack of mutant p53 mRNA expression in the normal tissues of this patient may be caused by decreased stability or decreased production. If this proves a more general pattern of expression of mutant p53 in individuals with germline mutations, these findings may explain the paucity of tumors in individuals affected with the Li-Fraumeni syndrome.

Adult↗
PubMed1992

Frequency and diversity of p53 mutations in childhood rhabdomyosarcoma.

The p53 gene was examined in primary or metastatic tumors from six patients with rhabdomyosarcoma (RMS) and in five RMS cell lines by screening methods including single-strand conformation polymorphism analysis, the RNase protection assay, sequencing of complementary DNA subclones, and Southern blotting. Six original tumors were of embryonal histology, four alveolar, and one mixed. p53 mutations were identified in four of the six tumors or cell lines derived from tumors with embryonal histology and in one of the four with alveolar histology. Consistent with p53 allele loss, each mutation was found in the homo- or hemizygous state. One tumor showed a G to C transversion at p53 codon 213 (arginine to proline), and another showed deletion of the entire gene. The p53 mutations in cell lines included a codon 248 C to T transition (arginine to tryptophan) in RD and a codon 280 A to T transversion (arginine to serine) in RH30. The cell line CTR contained a 4-base pair deletion at codons 219/220 in exon 6 with resultant frame shift and premature termination in exon 7. These data support the role of diverse types of p53 mutations in the pathogenesis and/or progression of a significant proportion of cases of childhood RMS.

Adolescent↗
PubMed1992

Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia.

The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. One pedigree was consistent with the Li-Fraumeni syndrome, and bone marrow from both diagnosis and remission indicated a germline G to T transversion at codon 272 (valine to leucine). Although members of another family were affected with leukemia, a 2-bp deletion in exon 6 was nonhereditary. The other two nonhereditary p53 mutations included a T to G transversion at codon 270 (phenylalanine to cysteine) and a G to C transversion at codon 248 (arginine to proline). These data support the role of both hereditary and acquired p53 mutations in the pathogenesis and/or progression of some cases of childhood acute lymphoblastic leukemia.

Adolescent↗
PubMed1992

Absence of hereditary p53 mutations in 10 familial leukemia pedigrees.

Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight families no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or mechanisms.

DNA, Neoplasm↗
PubMed1991

Characterization of acute lymphoblastic leukemia of childhood by immunoglobulin and T-cell receptor gene patterns.

Molecular biological studies of immunoglobulin (Ig) and T-cell antigen receptor (TCR) genes provide novel approaches to the identification and characterization of the acute lymphoblastic leukemias (ALL). Such studies greatly enhance our understanding of both the cells of origin in these diseases and the order of assembly of immune receptor genes in B-cells and T-cells. The patterns of Ig and TCR genes in B-cell precursor and T-cell ALL of childhood and ALL of infancy are heterogeneous though generally distinctive. The vast majority of cases of B-cell precursor ALL of childhood rearrange Ig heavy (H) chain genes, and 40-50% rearrange Ig light (L) chain genes. In contrast, in ALL of infancy, Ig genes are frequently germline, indicating generally less mature cells of origin in younger patients. Similarly, the vast majority of cases of T-cell ALL of childhood rearrange TCR delta, gamma, and beta genes and approximately one-half rearrange TCR alpha. TCR gene rearrangements are very common in cases of B-cell precursor ALL, but in patterns different from T-cells. In contrast, T ALL cells only infrequently rearrange Ig genes, and TCR gamma rearrangements are not found in ALL of infancy. The demonstration of lineage non-restricted Ig and TCR gene rearrangements raises questions about lymphocyte development and about the 'precursor' nature of ALL. The identification of generally distinctive patterns of these genes creates a foundation for their utilization as markers of minimal and preclinical disease. The extent to which specific immune receptor gene patterns correlate with clinical outcome in ALL warrants further study.

Child↗
PubMed1990

Characterization of the breakpoint of a t(14;14)(q11.2;q32) from the leukemic cells of a patient with T-cell acute lymphoblastic leukemia.

The leukemic cells and derivative cell line from a 74-year-old male with T-cell acute lymphoblastic leukemia showed chromosomal abnormalities including a t(14;14)(q11.2;q32). This translocation is characteristic of a variety of T-cell malignancies, particularly T-cell prolymphocytic leukemia and the clonal proliferations of peripheral T cells in patients with ataxia-telangiectasia. Using DNA probes that spanned the T-cell receptor alpha chain (TCRA) joining (J) locus, the DNA rearrangement caused by the translocation was identified, cloned, and sequenced. The breakpoint shows site-specific juxtaposition of a TCRA joining segment and DNA from a region of 14q32 centromeric to the immunoglobulin heavy chain locus. Comparison of restriction map and nucleotide sequence from this translocation with other related chromosomal breakpoints suggests a dispersion of breakpoints throughout the 14q32 region.

Amino Acid Sequence↗
PubMed1990

Characterization of immunoglobulin and T-cell receptor gene patterns in B-cell precursor acute lymphoblastic leukemia of childhood.

Immunoglobulin (Ig) and T-cell receptor (TCR) genes were examined in the lymphoblasts of 70 children with immunophenotypically defined B-cell precursor acute lymphoblastic leukemia (ALL). The most frequent genes to rearrange were Ig heavy (H) chain (93%) and TCR delta (79%), followed by TCR gamma (49%), Ig kappa and/or lambda light (L) chain (46%), TCR alpha (46%), and TCR beta (29%). Thus, despite their putative "B-cell precursor" lineage, these leukemias manifest a remarkably high incidence of TCR gene rearrangements. While certain patterns predominate, there is considerable heterogeneity in Ig and TCR genotypes in this disease. No significant associations were found between Ig and TCR genotype and commonly used prognostic factors including age, sex, race, WBC, French-American-British (FAB) subtype, or cytogenetics. However, the lymphoblasts of three of six patients who failed to achieve initial remission had germline patterns of every Ig and TCR gene, a genotype not observed in the leukemic cells from any of the 64 patients who achieved complete remission (p2 = .0007). This study suggests that particular Ig and TCR genotypes may be of clinical relevance in childhood B-cell precursor ALL. The finding of rearranged TCR genes in a large proportion of cases raises fundamental questions about early lineage commitment and lymphocyte differentiation along B-cell and T-cell pathways.

Adolescent↗
PubMed1987

Massive acute hemolysis secondary to Clostridium perfringens sepsis in a recently transfused oncology patient with multiple alloantibodies.

Sepsis with clostridia species is seen infrequently in oncology patients, and the massive acute intravascular hemolysis known to be associated with these organisms is rare. The urgency of making the diagnosis of clostridial sepsis is imperative since the course is rapidly fatal if untreated. We describe a patient with metastatic adenocarcinoma of the pancreas, known to have recent transfusions as well as multiple red cell alloantibodies, who developed massive nonimmunologic hemolysis associated with Clostridium perfringens sepsis. Because the hemolysis of C. perfringens sepsis can mimic that of a severe delayed hemolytic transfusion reaction, care must be taken to differentiate these conditions, especially in view of the frequency of transfusion in these patients as well as their predisposition to develop disseminated infections.

ABO Blood-Group System↗
PubMed1987

T cell receptor alpha-, beta-, and gamma-genes in T cell and pre-B cell acute lymphoblastic leukemia.

We examined alpha-, beta-, and gamma-T cell receptor (TCR) gene activation within acute lymphoblastic leukemias (ALLs) that represent early stages of B and T cell development. We wished to determine if TCR rearrangement and expression was lineage restricted, showed any developmental hierarchy, or could identify new subsets of T cells. Rearrangement of gamma and beta TCR genes occurred early in development but in no set order, and most T-ALLs (22/26) were of sufficient maturity to have rearranged both genes. T-ALLs preferentially rearranged C gamma 2 versus the C gamma 1 complex; no preference within the beta locus was apparent. Once rearranged, the beta TCR continued to be expressed (11/13), whereas the gamma TCR was rarely expressed (3/14). The alpha TCR was expressed only in more mature T-ALLs (8/14) that usually displayed T3. The 3A-1 T cell associated antigen appeared earliest in development followed by T11 and T3. Within pre-B cell ALL a higher incidence of lineage spillover was noted for gamma TCR rearrangements (8/17) than for beta rearrangements (3/17). This also contrasts with the only occasional rearrangement of immunoglobulin (Ig) heavy chains (3/25) in T-ALL. However, in pre-B ALL the pattern of gamma TCR usage was distinct from that of T cells, with the C gamma 1 complex utilized more frequently. Almost all ALLs could be classified as pre-B or T cell in type by combining Ig and TCR genes with monoclonal antibodies recognizing surface antigens, although examples of lineage duality were noted. Unique subpopulations of cells were discovered including two genetically uncommitted ALLs that failed to rearrange either Ig or TCR loci. Moreover, two T lymphoblasts were identified that possessed the T3 molecule but failed to express alpha plus beta TCR genes. These T-ALLs may represent a fortuitous transformation of T cell subsets with alternative T3-Ti complexes.

B-Lymphocytes↗
PubMed1987

Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy.

We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.

Acute Disease↗
PubMedDate not supplied

MLL genomic breakpoint distribution within the breakpoint cluster region in de novo leukemia in children.

PURPOSE: To assess translocation breakpoint distribution within the MLL genomic breakpoint cluster region (bcr), 40 cases of de novo leukemia in children were examined by karyotype and Southern blot analysis. PATIENTS AND METHODS: Criteria for inclusion were karyotypic or molecular rearrangement of chromosome band 11q23. Of the 40 cases, 31 occurred in infants. Twenty cases were acute lymphoblastic leukemia (ALL), 17 were acute myeloid leukemia (AML), and 3 were biphenotypic. RESULTS: Karyotype identified 27 cases with translocation of chromosome band 11q23 and 2 with abnormalities of band 11q13 but not 11q23. Southern blot analysis showed rearrangement within the MLL genomic bcr in 38 of the 40 cases. In these 38, additional probe-restriction digest combinations localized MLL genomic breakpoints to the 5' portion of the bcr in 14 cases and to the 3' portion in 18; material was insufficient for further localization to 5' or 3' within the bcr in 6 cases. In the two remaining cases, both with t(4;11)(q21;q23), one breakpoint mapped 5' of the bcr between intron 3 and exon 5, whereas the other breakpoint was neither within nor 5' of the MLL genomic bcr. CONCLUSIONS: Suggested trends warranting investigation in more patients were breakpoint sites in the 3' bcr in AML and in patients older than 12 months. The distribution of MLL genomic breakpoints within the bcr in de novo leukemia in children is distinct from that in adults, where the breakpoints cluster in the 5' portion of the bcr.

Acute Disease↗