Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple studies have documented an increased risk of secondary malignancies in patients receiving alkylating agents. Secondary leukemia following chemotherapy accounts for about 20% of all secondary neoplasms; most are acute nonlymphocytic. Secondary acute lymphoblastic leukemia has rarely been reported in either adult or childhood cancer. We report the development of acute T-cell lymphoblastic leukemia in a child following successful treatment of a paravertebral embryonal rhabdomyosarcoma (ERS). Southern blot analysis of DNA extracted from the T-cell lymphoblasts, using probes homologous to loci on the short arm of chromosome 11; P-calcitonin, P40.1 and H-ras, did not demonstrate the chromosomal loss of heterozygosity (LOH), a common feature of embryonal rhabdomyosarcoma. The data presented support the assumption that de novo leukemia emerged following treatment of the primary malignancy.
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PMID:T-cell acute lymphoblastic leukemia following therapy of rhabdomyosarcoma. 157 35

A panel of monoclonal antibodies was tested immunohistochemically to determine the utility of such reagents in distinguishing among metastatic carcinoma, lymphoma, leukemia and primary brain tumors. The monoclonal antibodies used were: (1) a cocktail comprised of three anti-glial fibrillary acidic protein antibodies (alpha-GFAP); (2) UJ13A, a panneuroectodermal antibody; (3) B72.3, which recognizes a carcinoma-distinctive tumor-associated glycoprotein complex; and (4) 2D1, a pan-leukocyte antibody. Fifty-three specimens (21 cerebrospinal fluids, 1 ventricular fluid, 2 brain cyst fluids, 12 needle washings, 15 imprints, 1 subdural fluid and 1 post-shunt fluid) were obtained from 21 gliomas, 2 meningiomas, 1 pineoblastoma, 11 metastatic tumors, 3 lymphomas, 1 leukemia and 14 cases without tumor. alpha-GFAP stained all 21 gliomas and 5 of 5 cases containing reactive brain fragments. UJ13A had a reactivity pattern similar to that of alpha-GFAP, but also stained the meningiomas, pineoblastoma, oat-cell carcinoma and embryonal rhabdomyosarcoma. B72.3 stained all adenocarcinomas and the large-cell carcinoma. 2D1 stained lymphoma and leukemia, all inflammatory cells and 4 of 12 glioblastomas. Although no single antibody was diagnostic of a specific tumor type, this panel accurately differentiated among most primary brain tumors, metastases, leukemias and lymphomas.
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PMID:The use of a panel of monoclonal antibodies in the evaluation of cytologic specimens from the central nervous system. 342 42

We investigated the frequency of p53 mutations in 19 pediatric cases of therapy-related leukemia or myelodysplastic syndrome. Eleven children presented with acute myeloid leukemia, one with mixed-lineage leukemia, two with acute lymphoblastic leukemia, and five with myelodysplasia at times ranging from 11 months to 9 years after a primary cancer diagnosis. The primary cancers, which included 11 solid tumors and eight leukemias, were treated with various combinations of DNA topoisomerase II inhibitors, alkylating agents, or irradiation. Leukemic or myelodysplastic marrows were screened for possible mutations by single-strand conformation polymorphism (SSCP) analysis of p53 exons 4 to 8. The only observed mutation was an inherited 2-basepair deletion at codon 209 in exon 6 that would shift the open reading frame, create a premature termination codon, and foreshorten the resultant protein. Prior therapy in this patient included DNA topoisomerase II inhibitors, alkylating agents, and irradiation. The secondary leukemia presented as myelodysplasia with monosomies of chromosomes 5 and 7 and abnormalities of chromosome 17. Although the primary cancer was an embryonal rhabdomyosarcoma and there was a family history of cancer, the case did not fulfill the clinical criteria for Li-Fraumeni syndrome. This study suggests that germline p53 mutations may predispose some children to therapy-related leukemia and myelodysplasia, but that p53 mutations otherwise are infrequent in this setting.
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PMID:The p53 gene in pediatric therapy-related leukemia and myelodysplasia. 863 98

Segmental jumping translocations are chromosomal abnormalities in treatment-related leukemias characterized by multiple copies of the ABL and/or MLL oncogenes dispersed throughout the genome and extrachromosomally. Because gene amplification potential accompanies loss of wild-type p53, we examined the p53 gene in a case of treatment-related acute myeloid leukemia (t-AML) with MLL segmental jumping translocation. The child was diagnosed with ganglioneuroma and embryonal rhabdomyosarcoma (ERMS) at 2 years of age. Therapy for ERMS included alkylating agents, DNA topoisomerase I and DNA topoisomerase II inhibitors, and local radiation. t-AML was diagnosed at 4 years of age. The complex karyotype of the t-AML showed structural and numerical abnormalities. Fluorescence in situ hybridization analysis showed multiple copies of the MLL gene, consistent with segmental jumping translocation. A genomic region including CD3, MLL, and a segment of band 11q24 was unrearranged and amplified by Southern blot analysis. There was no family history of a cancer predisposing syndrome, but single-strand conformation polymorphism (SSCP) analysis detected identical band shifts in the leukemia, ganglioneuroma, ERMS, and normal tissues, consistent with a germline p53 mutation, and there was loss of heterozygosity in the ERMS and the t-AML. Sequencing showed a CGA-->TGA nonsense mutation at codon 306 in exon 8. The results of this analysis indicate that loss of wild-type p53 may be associated with genomic instability after DNA-damaging chemotherapy and radiation, manifest as a complex karyotype and gene amplification in some cases of t-AML.
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PMID:Association of germline p53 mutation with MLL segmental jumping translocation in treatment-related leukemia. 961 38

Approximately 30% of malignant neoplasms in children are dysontogenetic tumors whose pathologic features resemble or recapitulate those of the developing organ or tissue of origin. Archetypes include classic neuroblastoma, Wilms' tumor, and embryonal rhabdomyosarcoma. This review traces the history of the principal types of dysontogenetic neoplasms and the primitive round cell tumors, Ewing's sarcoma, and peripheral primitive neuroectodermal tumor. Retinoblastoma, neuroblastoma, and Wilms' tumor were first described in the 19th century but with several different appellations than those we use today. Although some progress was made in the surgical management of Wilms' tumor during the 1940s and 1950s, most of these unique solid neoplasms of childhood were seen as essentially untreatable and inevitably fatal; surgery and perhaps irradiation were the principal therapeutic offerings. The folic acid analogue, aminopterin, was reported in 1948 as inducing the first complete but temporary remission in acute childhood leukemia. The chemotherapeutic era began shortly thereafter with effective chemotherapy in the management of Wilms' tumor with the introduction of dactinomycin. Pathologists were no longer restricted to being purveyors of the death sentence; they were now responsible for differentiating one type of primitive and embryonic neoplasm from another by using a variety of ancillary techniques, including tissue culture, electron microscopy, immunohistochemistry, and cytogenetics. Favorable or unfavorable morphologic types and subtypes of tumors were defined and, together with the pathologic staging, became incorporated into the therapeutic plan and prognostic assessment. During the past 40 years, these tumors progressed from being virtually treatment resistant to having an overall 5-year survival of 70% or greater. Through the cooperative efforts of pediatric hematologists/oncologists, pediatric surgeons, radiation therapists, and pathologists, the primitive and embryonic neoplasms of childhood are now viewed as some of the most treatable and curable of cancers.
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PMID:The evolution of the diagnosis and understanding of primitive and embryonic neoplasms in children: living through an epoch. 968 89

Childhood neoplasms are relatively rare and represent only about 1- 2% of the total incidence of neoplasms in United States. Concurrent episode of childhood cancer is uncommon and usually related to a cancer genetic syndrome. Li Fraumeni Syndrome refers to an autosomal dominant condition that is manifested by the development of certain cancers in early childhood and an increased lifetime risk for developing multiple primary cancers including sarcoma, breast cancer, leukemia, bone cancer, and others. We report a case of a 21-month-old girl who was found to have orbital embryonal rhabdomyosarcoma and adrenocortical tumor concurrently.
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PMID:A concurrent episode of two neoplasms in a toddler-age child. 2476 85

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome, with the characteristics of early onset of cancer and high cancer incidence. TP53 is widely accepted as a pathogenic gene of LFS. A 2 years and 6 months old boy is reported in this article, who was diagnosed with embryonal rhabdomyosarcoma (RMS) in the left submandibular region. His brother died of RMS, and his grandmother was diagnosed with breast cancer. TP53 gene mutation detection was performed in this patient and some family members, indicating a missense mutation in exon 8 of the patient: c.844C>T (p.Arg282Trp, heterozygous). TP53 mutation was also found in his mother and sister. The boy met the diagnostic criteria for LFS. Among pediatric patients, the most common LFS diseases include osteosarcoma, adrenocortical cancer, central nervous system tumor, and soft tissue tumor. Additionally, leukemia and lymphoma are also involved. LFS patients have a high risk to suffer secondary or even multiple cancers. Therefore, it is necessary to perform genetic detection for pediatric cancer patients, especially those with hereditary predisposition cancers. TP53 mutation often indicates poor prognosis, so it is important to take active treatment and systematic monitoring for LFS family.
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PMID:[A rhabdomyosarcoma patient from a Li-Fraumeni syndrome family: a case report and literature review]. 2923 27

The TP53 tumor-suppressor gene is mutated in >50% of human tumors and Li-Fraumeni patients with germ line inactivation are predisposed to developing cancer. Here, we generated tp53 deleted zebrafish that spontaneously develop malignant peripheral nerve-sheath tumors, angiosarcomas, germ cell tumors, and an aggressive Natural Killer cell-like leukemia for which no animal model has been developed. Because the tp53 deletion was generated in syngeneic zebrafish, engraftment of fluorescent-labeled tumors could be dynamically visualized over time. Importantly, engrafted tumors shared gene expression signatures with predicted cells of origin in human tissue. Finally, we showed that tp53del/del enhanced invasion and metastasis in kRASG12D-induced embryonal rhabdomyosarcoma (ERMS), but did not alter the overall frequency of cancer stem cells, suggesting novel pro-metastatic roles for TP53 loss-of-function in human muscle tumors. In summary, we have developed a Li-Fraumeni zebrafish model that is amenable to large-scale transplantation and direct visualization of tumor growth in live animals.
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PMID:tp53 deficiency causes a wide tumor spectrum and increases embryonal rhabdomyosarcoma metastasis in zebrafish. 3019 30