ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Myeloid leukemic progenitor cells proliferatein vitroin response to a variety of humoral factors, the most prominent among these being granulocyte-macrophage colony-stimulating factor (GM-CSF). The mechanism by which GM-CSF transduces its proliferative signal in acute myeloid leukemia has been extensively investigated over the past year. It is now known that the GM-CSF belongs to a new family of hematopoietic growth factor binding proteins which are charaterized by a relatively short intracytoplasmic domain that lacks a tyrosine kinase sequence. Nevertheless, studies performed using GM-CSF-dependent leukemic cell lines demonstrate the appearance of several new phosphotyrosine species after GM-CSF exposure, suggesting that receptor activation is directly or indirectly linked to tyrosine kinase stimulation. Apart from the basic biology of GM-CSF-induced signal transduction, the ability of this factor to enhance the S-phase fraction of myeloid leukemia blasts may have important therapeutic implications. Clinical trials are currently being conducted in an attempt to determine whether GM-CSF is able to overcome kinetic resistance of leukemic myeloblasts to cell cycle-specific agents such as cytarabine in the treatment of patients with acute myeloid leukemia.

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Adult T-cell leukemia/lymphoma is a disseminated malignancy of T lymphocytes infected by the human T-lymphotrophic virus type I. It is endemic in southern Japan, the Carribean basin, the southeastern United States, and central Africa. The virus is transmitted through intimate contact or exposure to blood products; only a small proportion of those infected develop adult T-cell leukemia/lymphoma. The malignant cells are activated T-helper cells that have suppressor function and multiple cytogenetic abnormalities. The disease occurs in mid to late life, years after exposure to the human T-lymphotrophic virus type I, with hypercalcemia, skin involvement, lymphadenopathy, hepatospenomegaly, lytic bone lesions, and leukemia. Although the disease usually has a rapidly progressive clinical course, there is a spectrum of clinical and pathologic features with smoldering and subacute forms. Our knowledge of this malignancy has grown rapidly and is leading to greater understanding of the relationships between human retroviruses and oncogenes.

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Modern treatments and supportive care regimens for acute myeloid leukemia have produced some cures of what was once a uniformly fatal disease. To enhance the cure rate, intense efforts are now being put forth to understand the mechanisms of resistance to chemotherapeutic regimens that actually arise in clinical cases of acute myeloid leukemia, and to develop ways and means to circumvent such resistance. This review focuses on such efforts involving daunorubicin and cytarabine, the two most effective agents currently available for treatment of the disease. Most current published studies of daunorubicin have focused on detecting the classic form of multidrug resistance. For cytarabine, pharmocologically directed treatment approaches and enhancement of cytarabine leukemic cell kill by increasing the distribution of cells in S-phase and manipulating cellular cytarabine transport are currently under investigation.

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Using intensive induction chemotherapy, primarily with combinations of an anthracycline and cytarabine, complete remission rates of greater than 70% are now achieved in patients with acute myeloid leukemia under the age of 60 years. The treatment of elderly patients with acute myeloid leukemia is difficult and remains controversial. The prognosis for both adults and children with acute lymphoblastic leukemia has improved as more extensive chemotherapy regimens have been used. Recently, a group of leukemias have been identified that have features of both acute lymphoblastic leukemia and acute myeloid leukemia, and these are referred to as biphenotypic or hybrid leukemias. These hybrid leukemias represent an important subgroup, which appears to have a worse outcome regardless of the therapy administered.

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Improvement in therapies for childhood acute lymphocytic leukemia has resulted in cure for the majority of young people with this disease. Recent therapeutic advances have focused on testing more extensive treatments for cases with adverse clinical/biologic features, or pharmocologic studies to maximize dose intensity. The latter includes a trial of alternating high-dose intravenous methotrexate with high-dose intravenous 6-mercaptopurine given for the first year postremission in an attempt to circumvent the patient's natural variability of absorption and metabolism of these drugs. Patients with acute myeloid leukemia continue to fare much worse and only one in three are long-term survivors. Acute myeloid leukemia therapies emphasize the use of intensive toxic courses of cytarabine, etoposide, and an anthracycline to cytoreduce the leukemic clone. Acute progranulocytic leukemia, however, now appears to be responsivein vitroto the differentiation agent all-trans retinoic acid. For this disease, complex responses are now obtained without the use of conventional antineoplastics.

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The myelodysplastic syndromes are clonal hematopoietic stem cell disorders characterized by varying degress of pancytopenia and often a progression to acute myeloid leukemia. Recent evidence has linked myelodysplastic syndromes to environmental and occupational genotoxic exposure. Specific cytogenetic abnormalities are well described in myelodysplastic syndromes and have been demonstrated to be useful diagnostic and prognostic tools. Activation of protoonco genes such asrasandfmshave also been noted in myelodysplastic syndromes; however, their contribution to the pathogenesis of the syndrome remains to be determined. Aggressive leukemia-like induction therapy, differentiating agents (low-dose cytarabine, 13-cis-retinoic acid) have had little impact on overall survival in myelodys plastic syndromes. The recombinant hematopoietic growth factors (granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor) may be of significant benefit to patients with myelodysplastic syndromes, although it remains to be determined whether they will have a substantial impact on survival. Allogeneic bone marrow transplantation is the only potentially curable treatment of myelodysplastic syndromes. The advanced age of these patients as well as the lack of histocompatible donors restricts this modality to only a small proportion of patients.

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The chronic lymphoid leukemias are a heterogeneous group of disorders with different immunologic, biologic, and clinical features. The most common of these are the B-cell diseases, chronic lymphocytic leukemia and its variants, including prolymphocytic leukemia and hairy cell leukemia. The increased use of immunophenotyping has identified a number of other less common but related disorders. Despite being clonal disorders, the chronic B-cell leukemias exhibit immunologic abnormalities in multiple other lineages, the mechanism for which is not clear. Fludarabine, 2'-deoxycoformycin, and 2-chlorodeoxyadenosine are purine analogues that have advanced the treatment of chronic B-cell leukemias. Fludarabine appears to be the single most effective agent for chronic lymphocytic leukemia, while 2'-deoxycoformycin and 2-chlorodeoxyadenosine are both extremely effective in hairy cell leukemia. A recently completed comparison of α-interferon with 2'-deoxycoformycin in hairy cell leukemia may redefine the standard therapy for this disorder. Continued interaction between laboratory and clinical scientists is essential for continued progress in these diseases.

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The past year has seen important advances in our understanding of the molecular biology of human cancer. We have learned more about how normal genes with critical functions in growth and development can induce cellular transformation and malignancy if mutated or overexpressed. The finding of such oncogenes in specific human cancers often portends a poor prognosis. We have learned more about tumor suppressor genes, whose loss by mutation, deletion, or translocation can lead to cancer. A series of defects involving both oncogenes and tumor suppressor genes has been shown to characterize the multistep development of a fully malignant colon cancer. We have new insights into the promotion of malignancy by the fused gene product resulting from the chromosomal abnormality diagnostic of one leukemia, chronic myelogenous leukemia. Recently, in acute promyelocytic leukemia, a characteristic chromosomal abnormality has been shown to result in a specific fusion of a nuclear receptor that activates transcription and a previously unknown gene. Most interestingly, a ligand for this rearranged receptor has been shown to be a novel effective treatment for the disease. This review summarizes many of these advances.

ISSN:1040-8746    

出版商:OVID    

年代:1991

数据来源: OVID