Leukemia Research and Treatment最新文献

Adult T-cell leukemia (ATL) is a leukemia derived from mature CD4(+) T cells and induced by human T-cell leukemia virus type 1 (HTLV-1) infection. Previous studies have revealed many possible molecular and cellular mechanisms of HTLV-1-induced leukemogenesis, but it still remains unknown how HTLV-1 transforms peripheral CD4 T cells in infected individuals. Given the fact that only 2-5% of infected individuals develop ATL, HTLV-1 infection alone is not sufficient for the transformation of infected cells. Host genetic and epigenetic abnormalities and host immunological status should be considered in attempting to understand the mechanism of the oncogenesis of ATL. Nonetheless, it is obvious that HTLV-1 infection dramatically increases the risk of leukemia generation from peripheral CD4 T-cells, in which the incidence of leukemia is quite low. Furthermore, the evidence that all ATL cases retain the HTLV-1 provirus, especially the 3' region, indicates that HTLV-1-encoded genes play a critical role in leukemogenesis. Since increasing evidence indicates that the HTLV-1 bZIP factor (HBZ) gene plays a significant role in the pathogenesis of HTLV-1, we will discuss the cellular and molecular mechanism of ATL generation from the virological point of view, particularly focusing on HBZ.

Interleukin 10 (IL10) is a pleiotropic cytokine that stimulates various hematopoietic cells. The tumor necrosis factor alpha (TNFα) is a cytokine that may influence the transcriptional activity induced by glucocorticoids. This study examined the impact of TNFα (G308A) and IL10 (G1082A) polymorphisms at promoter regions in relation to the overall survival of 105 children (0 ≤ 18 years) with acute lymphoblastic leukemia (ALL) for a period of 126 months, treated according to the protocol GBTLI99. The G1082A and G308A polymorphisms were identified by allele-specific PCR and PCR-RFLP, respectively. Patients with IL10AA genotype had a higher death ratio (44%, P = 0.0089). Patients with both IL10AA and TNFAA genotypes showed the worst survival when compared with the IL10GG and TNFGA genotypes (P = 0.0043). The results of this study revealed a lower survival among patients with IL10AA genotype and the concomitant occurrence of IL10AA and TNFAA genotypes.

Algae preparations are commonly used in alternative medicine. We examined the effects of algae extracts on normal hematopoietic cells and leukemia cells. Ethanol extracts were prepared of Dunaliella salina (Dun), Astaxanthin (Ast), Spirulina platensis (Spir), and Aphanizomenon flos-aquae (AFA). Cell viability effects were completed by Annexin staining. Ast and AFA inhibited HL-60 and MV-4-11 whereas Dun and Spir had no effect. Primary AML blasts demonstrated increased apoptosis in AFA. Primary CLL cells showed apoptosis at 24 hours after exposure to Dun, Ast, Spir, and AFA. High AFA concentrations decreased viability of normal marrow cells. Normal CD34+ viability was inhibited by Dun. Dun and AFA inhibited BFU-E, but all extracts inhibited CFU-GM. Cell-cycle analysis of AML cell lines showed G0/G1 arrest in the presence of AFA. These data suggest that algae extracts may inhibit AML cell lines and leukemia blasts, but they may also have potential inhibitory effects on normal hematopoiesis.

The t(9;22)(q34;q11) translocation is found in about 90% of chronic myeloid leukemia (CML) patients. About 5-10% of CML patients have complex variant translocations involving a third chromosome in addition to chromosomes 9 and 22. Herein, we describe a CML-chronic phase male with a complex translocation involving chromosome 16, t(9;22;16)(q34;q11;q24). First, he was treated with interferon-alpha and intermittent hydroxyurea, but only a partial cytogenetic response was attained. Subsequently, the patient was treated with imatinib mesylate because of an additional chromosome abnormality, trisomy 8. A major molecular response was obtained after one year's imatinib therapy, and the follow-up chromosomal analysis performed 4 years and 3 months after the initiation of imatinib therapy displayed a normal karyotype of 46,XY.

Myeloid sarcoma (MS) is a neoplasm of immature granulocytes, monocytes, or both involving any extramedullary site. Twenty one patients with MS at diagnosis who were treated at King Hussein Cancer Center in Jordan were included in this retrospective study with a male to female ratio of 2 : 1. The most common site was the reticuloendothelial system. The most common morphology subtype was M2 (38%) and the most frequent chromosomal abnormality was trisomy 8. Twenty patients received induction chemotherapy; only 14 (70%) achieved complete remission. Median survival time was 24.7 months for the whole group and 58.6 months for patients who underwent allogenic bone marrow transplant. This paper showed that MS has frequent M2 morphology, carries chromosomal aberrations other than t(8;21), and requires aggressive therapy as a front line approach.

Among herpesviruses, γ-herpesviruses are supposed to have typical oncogenic activities. Two human γ-herpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), are putative etiologic agents for Burkitt lymphoma, nasopharyngeal carcinoma, and some cases of gastric cancers, and Kaposi's sarcoma, multicentric Castleman's disease, and primary effusion lymphoma (PEL) especially in AIDS setting for the latter case, respectively. Since such two viruses mentioned above are highly species specific, it has been quite difficult to prove their oncogenic activities in animal models. Nevertheless, the viral oncogenesis is epidemiologically and/or in vitro experimentally evident. This time, we investigated gene expression profiles of KSHV-oriented lymphoma cell lines, EBV-oriented lymphoma cell lines, and T-cell leukemia cell lines. Both KSHV and EBV cause a B-cell-originated lymphoma, but the gene expression profiles were typically classified. Furthermore, KSHV could govern gene expression profiles, although PELs are usually coinfected with KSHV and EBV.

It has been revealed that the Wnt/β-catenin signaling pathway plays an important role in the development of solid tumors and hematological malignancies, particularly in B-cell neoplasia and leukemia. In the last decade there have been made experimental approaches targeting the Wnt pathway in chronic leukemia. In this paper we provide an overview about the current state of knowledge regarding the Wnt/β-catenin signaling pathway in chronic leukemia with special focus on therapeutic options and strategies.

Recent studies have shown genetic and epigenetic aberrations resulting in aberrant activation of the Wingless-Int (Wnt) pathway, thus influencing the initiation and progression of acute myeloid leukemia (AML). Of major importance, these findings may lead to novel treatment strategies exploiting targeted modulation of Wnt signaling. This paper comprises the latest status of knowledge concerning the role of Wnt pathway alteration in AML and outlines future lines of research and their clinical perspectives.

Myeloid Sarcoma may occur in patients with an acute or chronic myeloproliferative disorder as well as de novo, with no apparent sign or symptom of concomitant haematological disease. The patients are preferentially young male and the site of disease localization may vary from central nervous system to pleura and thorax, with a common involvement of the reticuloendothelial system. The disease often shows chromosomal rearrangements, involving chromosomes 7, 8 and 3 and sometimes a complex karyotype (more than 3 abnormalities) is detected at diagnosis. The prognosis of this disease is dismal and only high-dose chemotherapy with autologous or allogeneic stem cells transplantation (auto or allo-SCT) may be potentially curative. In the absence of definitive elements that can define the prognosis of extra-medullary localization of "standard risk" AML, Clinicians should pursue the collection of data from different Centres and design of homogeneous treatment strategies, that could integrate standard chemotherapy with specific approaches, such as radiotherapy, transplant procedures or, in selected cases (such as those displaying molecular abnormalities involving protein tyrosine-kinases), molecularly targeted therapies.