Acute Leukemia Virus Research Articles

MYB as a Critical Transcription Factor and Potential Therapeutic Target in AML.

Myb was identified over four decades ago as the transforming component of acute leukemia viruses in chickens. Since then it has become increasingly apparent that dysregulated MYB activity characterizes many blood cancers, including acute myeloid leukemia, and that it represents the most "addictive" oncoprotein in many, if not all, such diseases. As a consequence of this tumor-specific dependency for MYB, it has become a major focus of efforts to develop specific antileukemia drugs. Much attention is being given to ways to interrupt the interaction between MYB and cooperating factors, in particular EP300/KAT3B and CBP/KAT3A. Aside from candidates identified through screening of small molecules, the most exciting prospect for novel drugs seems to be the design of peptide mimetics that interfere directly at the interface between MYB and its cofactors. Such peptides combine a high degree of target specificity with good efficacy including minimal effects on normal hematopoietic cells.

CAR-T Therapy: A Promising Cancer Treatment

CAR-T therapy is a new clinical treatment option. It is the focus of an increasing number of researches, all of which suggested that it has a beneficial therapeutic effect on a variety of diseases, especially blood cancer. In this paper, clinic applications of CAR-T therapy for many diseases are listed, including B-cell acute lymphoblastic leukemia, Hepatitis B, and Human Immunodeficiency Virus. The differences between CAR-T therapy and other cancer treatments like tumor-infiltrating lymphocyte and T cell receptor therapy were discussed, standard biological medicines, and antibody-mediated anti-cancer drugs. The study also looks at the limitations and side-effects of CAR-T therapy, such as toxicity, and missing the target. The disadvantages, constraints, and options for improvement were also discussed in the paper. To summarize, CAR-T therapy has a good therapeutic function on some illnesses, although it is still in the experimental stage and is not commonly used in the clinic. In the near future, CAR-T therapy is likely to be used in a rising range of therapeutic therapies. In general, this paper can help get a better knowledge of CAR-T treatment, as well as a more exact comprehension of its future evolution.

Clinical characteristics and evolution of pediatric patients with acute leukemia and SARS-COV2 virus infection in a third level hospital in Mexico

IntroductionReports have revealed that people susceptible to severe forms of COVID-19 are older adults with comorbidities; However, the pediatric population has also been affected, considering children with underlying conditions such as onco-hematological conditions to be high risk. We present a cases series in a third level hospital. Material and methodsWe conducted a retrospective study in children under the age of 16 years with a diagnosis of acute leukemia and infection with the SARS-CoV2 virus. Descriptive statistics with means and percentages were used. To show differences between the groups, Chi-square test, Student t test and Mann-Whitney U test were used depending on the type of variable and its distribution. ResultsSARS-CoV2 virus infection was confirmed in 15 children diagnosed with acute leukemia, at different stages of treatment. The mean age was 7.5 years, 8 male and 7 female, 11 of them diagnosed with acute B-cell lymphoblastic leukemia, one with acute T-cell lymphoblastic leukemia and 3 with acute myeloid leukemia. The mean days of hospital stay at the diagnosis of COVID-19 was 22. Thirteen of the children had fever and neutropenia. 7 patients died. There was a statistically significant correlation with the outcome in patients who presented a prolongation of aPTT, an increase in D-dimer, an increase in liver enzymes and severe respiratory distress with the need for mechanical ventilation. ConclusionThe risk of death in children with leukemia and COVID-19 was associated with prolonged aPTT, increased D-dimer, increased liver enzymes, respiratory distress, and the need for mechanical ventilation.

THE CHANGES IN BLOOD PARAMETERS OF COWS INFECTED BY LEUCOSIS IN CASE OF COMPLICATIONS WITH ACUTE ANAPLASMOSIS

The authors found out that some districts of the Tomsk region are unfavourable in respect to bovine anaplasmosis. In enzootic areas with bovine anaplasmosis the bovine leukemia was observed in susceptible animals. The research focuses on hematological and immunological changes of the blood of cows infected with leukemia during the acute anaplasmosis. That was found out in spring while intense activity of ixodids (the end of April). The researchers arranged two groups of Black-and-White cows aged 2.5-3 years infected with leukemia virus. The 1st group was infected with acute anaplasmosis cow leukemia virus, the 2nd group (control) was infected with anaplasm-free cow leukemia virus. The changes in the hematological pattern of cows infected with leucosis in case of complications with acute anaplasmosis consist in eosinophilia, neutropenia, lymphocytosis and monocytopenia. The changes in the immune system of cows were less noticeable and characterized by a moderate increase in IgG and high titers of antibodies to leukemia virus. The researchers assume that there is a significant sensitization of the humoral component of the immune system of cows infected with leucosis in case of complications with acute anaplasmosis. The noticeable lymphocytosis in the certain cows infected with leukemia virus in case of complications with acute anaplasmosis should be taken into account when making a diagnosis for cattle leukemia. This occurence in the hematological picture of blood can be characterized as a temporary leukemia reaction, causing a false positive result of hematological test on leukemia.

Saint-Petersburg experience of allogeneic hematopoietic stem cell transplantation in patients with acute leukemia and human immunodeficiency virus

Saint-Petersburg experience of allogeneic hematopoietic stem cell transplantation in patients with acute leukemia and human immunodeficiency virus

SPARC promotes leukemic cell growth and predicts acute myeloid leukemia outcome

Aberrant expression of the secreted protein, acidic, cysteine-rich (osteonectin) (SPARC) gene, which encodes a matricellular protein that participates in normal tissue remodeling, is associated with a variety of diseases including cancer, but the contribution of SPARC to malignant growth remains controversial. We previously reported that SPARC was among the most upregulated genes in cytogenetically normal acute myeloid leukemia (CN-AML) patients with gene-expression profiles predictive of unfavorable outcome, such as mutations in isocitrate dehydrogenase 2 (IDH2-R172) and overexpression of the oncogenes brain and acute leukemia, cytoplasmic (BAALC) and v-ets erythroblastosis virus E26 oncogene homolog (ERG). In contrast, SPARC was downregulated in CN-AML patients harboring mutations in nucleophosmin (NPM1) that are associated with favorable prognosis. Based on these observations, we hypothesized that SPARC expression is clinically relevant in AML. Here, we found that SPARC overexpression is associated with adverse outcome in CN-AML patients and promotes aggressive leukemia growth in murine models of AML. In leukemia cells, SPARC expression was mediated by the SP1/NF-κB transactivation complex. Furthermore, secreted SPARC activated the integrin-linked kinase/AKT (ILK/AKT) pathway, likely via integrin interaction, and subsequent β-catenin signaling, which is involved in leukemia cell self-renewal. Pharmacologic inhibition of the SP1/NF-κB complex resulted in SPARC downregulation and leukemia growth inhibition. Together, our data indicate that evaluation of SPARC expression has prognosticative value and SPARC is a potential therapeutic target for AML.

Production of L-glutaminase and its optimization from a novel marine isolate Vibrio azureus JK-79

L-Glutaminase is an amidohydrolase which is produced by a variety of micro-organisms including bacteria, yeast and fungi. It is currently used in the treatment of acute lymphoblastic leukemia (ALL) and human immunodeficiency virus (HIV). Another potential application of L-glutaminase is as flavor enhancing agent in soy sauce fermentation. Even though L-glutaminase activity was reported in numerous micro-organisms, production of L-glutaminase from marine bacteria is very scanty. With this view, in the present research work, L-glutaminase production pattern was studied under submerged fermentation using novel marine isolate Vibrio azureus strain JK-79 (GenBank Acession Number JQ820323) based on one-factor-at-a-time approach. The maximum yield of enzyme production (247 U/ml) was achieved in a seawater based medium at pH 8, 37°C, 1% inoculum concentration and 2% glutamine concentration for 24 h. The medium when supplemented with carbon source, it improved the enzyme production from 247 to 321 U/ml with 1.5% maltose. Addition of 2% soybean meal also improved the L-glutaminase production (289 U/ml). The above results indicate the scope for production of salt tolerant L-glutaminase using this novel marine bacterial strain. Keywords: L-Glutaminase, Vibrio azureus JK-79, submerged fermentation, optimization of fermentation, one-factor-at-a-time approach . Afr. J. Biotechnol Vol. 12 No. 50

Role of MYC in Medulloblastoma.

Since its discovery as an oncogene carried by the avian acute leukemia virus MC29 in myelocytomatosis (Roussel et al. 1979) and its cloning (Vennstrom et al. 1982), c-MYC (MYC), as well as its paralogs MYCN and MYCL1, has been shown to play essential roles in cycling progenitor cells born from proliferating zones during embryonic development, and in all proliferating cells after birth. MYC deletion induces cell-cycle exit or cell death, depending on the cell type and milieu, whereas MYC and MYCN amplification or overexpression promotes cell proliferation and occurs in many cancers. Here, we review the relationship of MYC family proteins to the four molecularly distinct medulloblastoma subgroups, discuss the possible roles MYC plays in each of these subgroups and in the developing cells of the posterior fossa, and speculate on possible therapeutic strategies targeting MYC.

Analysis of Fatal Cases of Pandemic Influenza A (H1N1) Virus Infections in Pediatric Patients with Leukemia

Background: Pandemic influenza A/H1N1/2009 virus usually causes mild illness in healthy children. Chronic medical conditions are recognized as increasing the risk for complications of influenza virus infection. Although most studies including children with acute leukemia and H1N1 virus have reported no deaths, some anectodal reports with low patient numbers have reported mortality rates as high as 28.5%. Here, we report patients with leukemia and H1N1 virus and review the literature. Methods: Medical records of all children with leukemia and H1N1 virus in our institution were reviewed for demographic, clinical, and laboratory data. We also carried out a systematic review of the English-language literature. Among the 24 articles found, only patients with leukemia and pandemic H1N1 infections were reviewed by two independent reviewers. Results: Eight of 98 children who received chemotherapy for leukemia were diagnosed with pandemic H1N1 infection. One developed pneumonia and acute respiratory distress syndrome (ARDS) and died. Another one developed hemophagocytic lymphohistiocytosis (HLH) and died due to secondary infection during the 6th week of treatment for HLH. In our study, 2 of 8 patients had a fatal course (25%), compared with an overall mortality of 2.5% in the studies retrieved from PubMed (6/232). Conclusion: Pandemic H1N1 influenza virus caused mortality in patients with ARDS or HLH; an unexpected finding for pandemic H1N1 (2009) influenza virus. Thus, for children with leukemia and infected with H1N1 virus, short- and long-term complications should be kept in mind during evaluation.

Crk and Abi1: Binary Molecular Switches That Regulate Abl Tyrosine Kinase and Signaling to the Cytoskeleton

The nonreceptor tyrosine kinases Abl and Arg are among the most well-characterized tyrosine kinases in the human genome. The activation of Abl by N-terminal fusions with Bcr (Bcr-Abl) or Gag (v-Abl) is responsible for chronic myeloid leukemia or Ph+ acute lymphoblastic leukemia and mouse leukemia virus, respectively. In addition, aberrant Abl and Arg activation downstream of several oncogenic growth factor receptors contributes to the development and progression of a variety of human cancers, often associated with poor clinical outcome, drug resistance, and tumor invasion and metastasis. Abl activation can occur by a variety of mechanisms that include domain interactions involving structural remodeling of autoinhibited conformations as well as direct phosphorylation by upstream kinases and phosphatases. Constitutive activation of Abl plays a significant role in regulating the actin cytoskeleton by modulating cell adhesion, motility, and invadopodia. This review addresses the role of Abl and Arg in tumor progression with particular emphasis on the roles of Crk and Abi1 adapter proteins as distinct molecular switches for Abl transactivation. These insights, combined with new insights into the structure of these kinases, provide the rationale to envision that Crk and Abi1 fine-tune Abl regulation to control signaling to the cytoskeleton.

Cell Transformation by RNA Viruses: An Overview

Studies of oncogenic viruses have made seminal contributions to the molecular biology of cancer. Key discoveries include the identification of viral oncogenes and cellular proto-oncogenes, elucidation of signal transduction pathways, and identification of tumor suppressor genes. The origins of cancer virology began almost exactly one hundred years ago with the discovery of avian sarcoma and acute leukemia viruses—RNA-containing viruses of the retrovirus family. The study of animal cancer viruses accelerated beginning in the late 1960s and early 1970s, with the discovery of DNA viruses that could transform cells in culture, and the development of quantitative assays for transformation by DNA and RNA-containing tumor viruses. The discovery of reverse transcriptase in retroviruses in 1970 also greatly accelerated research on these viruses. Indeed RNA and DNA tumor viruses led the way in cancer molecular biology during this era before molecular cloning. It was possible to physically purify virus particles and generate specific hybridization probes for viral DNA and RNA at a time when it was not possible to analyze cellular genes in the same manner. [...]

The Level of Friend Retrovirus Replication Determines the Cytolytic Pathway of CD8+T-Cell-Mediated Pathogen Control

Cytotoxic T cells (CTL) play a central role in the control of viral infections. Their antiviral activity can be mediated by at least two cytotoxic pathways, namely, the granule exocytosis pathway, involving perforin and granzymes, and the Fas-FasL pathway. However, the viral factor(s) that influences the selection of one or the other pathway for pathogen control is elusive. Here we investigate the role of viral replication levels in the induction and activation of CTL, including their effector potential, during acute Friend murine leukemia virus (F-MuLV) infection. F-MuLV inoculation results in a low-level infection of adult C57BL/6 mice that is enhanced about 500-fold upon coinfection with the spleen focus-forming virus (SFFV). Both the low- and high-level F-MuLV infections generated CD8+ effector T cells that were essential for the control of viral replication. However, the low-level infection induced CD8+ T cells expressing solely FasL but not the cytotoxic molecules granzymes A and B, whereas the high-level infection resulted in induction of CD8+ effector T cells secreting molecules of the granule exocytosis pathway. By using knockout mouse strains deficient in one or the other cytotoxic pathway, we found that low-level viral replication was controlled by CTL that expressed FasL but control of high-level viral replication required perforin and granzymes. Additional studies, in which F-MuLV replication was enhanced experimentally in the absence of SFFV coinfection, supported the notion that only the replication level of F-MuLV was the critical factor that determined the differential expression of cytotoxic molecules by CD8+ T cells and the pathway of CTL cytotoxicity.

WS5, a direct target of oncogenic transcription factor Myc, is related to human melanoma glycoprotein genes and has oncogenic potential

We have isolated a gene (WS5) that is specifically expressed at the mRNA and protein level in avian fibroblasts transformed by the v-myc oncogene of avian acute leukemia virus MC29. In a conditional cell transformation system, WS5 gene expression was tightly correlated with v-myc activation. The WS5 gene contains 11 exons, encoding a 733-amino acid protein with a transmembrane region and a polycystic kidney disease (PKD) domain. Near the transcriptional start site, the WS5 promoter contains a cluster of four binding sites for the Myc-Max complex and a binding site for transcription factor C/EBPalpha. Electrophoretic mobility shift assays and chromatin immunoprecipitation showed that Myc, Max and C/EBPalpha bind specifically to these sites. Functional promoter analyses revealed that both the Myc-binding site cluster and the C/EBPalpha-binding site are essential for strong transcriptional activation, and that Myc and C/EBPalpha synergistically activate the WS5 promoter. Ectopic expression of WS5 led to cell transformation documented by anchorage-independent growth. The human melanoma antigen Pmel17, a type I transmembrane glycoprotein, is the mammalian protein with the highest amino acid sequence identity (38%) to WS5. The Pmel17 gene is regulated by the MITF protein, a bHLHZip transcription factor with DNA binding specificities similar to those of Myc/Max. WS5 is also related to human glycoprotein GPNMB expressed in metastatic melanoma cells and implicated in the progression of brain and liver tumors.

Cooperative cell transformation by Myc/Mil(Raf) involves induction of AP-1 and activation of genes implicated in cell motility and metastasis

Avian fibroblasts transformed simultaneously by the v-myc and v-mil(raf) oncogenes of acute leukemia and carcinoma virus MH2 contain elevated levels of c-Fos and c-Jun, major components of the transcription factor complex AP-1. To define specific transcriptional targets in these cells, subtractive hybridization techniques were employed leading to the identification of strongly upregulated genes including OPN (osteopontin), 126MRP, and rac2. OPN is a cytokine and cell attachment protein which has been implicated in human tumor progression and metastasis, the calcium binding 126MRP protein is related to the human S100 protein family involved in invasive cell growth, and the Rac2 protein belongs to the Rho family of small GTPases regulating actin reorganization and cell migration. Promoter analysis indicated that OPN activation is mediated by a non-consensus AP-1 binding site located close to the transcription start site. Electrophoretic mobility shift assays, chromatin immunoprecipitation and transcriptional reporter gene analyses showed that c-Fos and c-Jun bind specifically to this site and that c-Fos efficiently transactivates the OPN promoter. High-level expression of OPN, 126MRP, or Rac2 proteins from a retroviral vector led to partial cell transformation, documented by morphological changes and anchorage-independent growth. The specific activation in v-myc/v-mil(raf)-transformed cells of target genes with intrinsic oncogenic potential may provide an explanation for the longstanding observation that concomitant expression of these oncogenes leads to strongly enhanced oncogenicity in vivo and in vitro compared to cell transformation by v-myc or v-mil(raf) alone.

Inhibition of HTLV-1 transcription by cyclin dependent kinase inhibitors.

HTLV-1 is the etiologic agent for adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), where viral replication and transformation are largely dependent upon modification of regulatory and host cell cycle proteins. The mechanism of HTLV-1 transformation appears to be distinct from that of many known chronic or acute leukemia viruses and is related to the viral activator Tax. Here we show that cyclin E, can associate tightly with the coactivator p300 and Pol II complex in HTLV-1 infected cells. The cyclin E associated complex is kinase active and phosphorylates the carboxy terminal domain of RNA Pol II. More importantly, p21/Waf1, a well-known cdk inhibitor at the G1/S border, inhibits transcription of HTLV-1 in both transfections and in in vitro transcription assays. Finally, specific cdk chemical inhibitors, functionally similar to cellular cdkIs, such as p21/Waf1 which inhibits cyclin E/cdk2 activity, also inhibit transcription of the HTLV-1 promoter. In particular, Purvalanol A, with an IC50 of 0.035 microm inhibits activated, but not basal transcription, as well as HTLV-1 infected cells. Collectively, the role of cyclin E/cdk2 in HTLV-1 infected cells and its involvement in RNA Pol II phosphorylation is discussed.

Avian Models to Study the Transcriptional Control of Hematopoietic Lineage Commitment and to Identify Lineage-Specific Genes

E26 is an avian acute leukemia virus with a profound ability to transform multipotent hematopoietic progenitor cells both in vivo and in vitro. Progenitor cells transformed by this virus can be expanded in vitro as undifferentiated clones for up to two months and can also be induced to differentiate into cells of the erythroid, eosinophilic, thrombocytic, and myelomonocytic lineages with reproducible kinetics. Aside from the proliferative stimulus provided by the E26 oncoprotein, these cells are remarkably similar to normal hematopoietic progenitors. They therefore provide an ideal assay system for determining the influence of ectopically expressed transcription factors on both maturation and commitment to several hematopoietic lineages. Results from experiments using this system suggest that subtle shifts in the balance of lineage-restricted transcription factors can result in profound changes in phenotype and challenge the notion that lineage commitment is a uni-directional process. Analysis of the regulatory elements governing the expression of these genes has provided novel mechanistic insights into the transcriptional control of hematopoiesis. In addition to their utility in deciphering the control of lineage commitment, the ability to grow large numbers of undifferentiated and more mature hematopoietic cells has facilitated the discovery of a number of novel, lineage-restricted genes. Analysis of the proteins encoded by these genes is helping to clarify the role of a number of membrane proteins in the interaction between hematopoietic cells and their microenvironments.

Common properties of nuclear body protein SP100 and TIF1alpha chromatin factor: role of SUMO modification.

The SP100 protein, together with PML, represents a major constituent of the PML-SP100 nuclear bodies (NBs). The function of these ubiquitous subnuclear structures, whose integrity is compromised in pathological situations such as acute promyelocytic leukemia (APL) or DNA virus infection, remains poorly understood. There is little evidence for the occurrence of actual physiological processes within NBs. The two NB proteins PML and SP100 are covalently modified by the ubiquitin-related SUMO-1 modifier, and recent work indicates that this modification is critical for the regulation of NB dynamics. In exploring the functional relationships between NBs and chromatin, we have shown previously that SP100 interacts with members of the HP1 family of nonhistone chromosomal proteins and that a variant SP100 cDNA encodes a high-mobility group (HMG1/2) protein. Here we report the isolation of a further cDNA, encoding the SP100C protein, that contains the PHD-bromodomain motif characteristic of chromatin proteins. We further show that TIF1alpha, a chromatin-associated factor with homology to both PML and SP100C, is also modified by SUMO-1. Finally, in vitro experiments indicate that SUMO modification of SP100 enhances the stability of SP100-HP1 complexes. Taken together, our results suggest an association of SP100 and its variants with the chromatin compartment and, further, indicate that SUMO modification may play a regulatory role in the functional interplay between the nuclear bodies and chromatin.

Ets and retroviruses - transduction and activation of members of the Ets oncogene family in viral oncogenesis.

Studies of retroviral-induced oncogenesis in animal systems led to the initial discovery of viral oncogenes and their cellular homologs, and provided critical insights into their role in the neoplastic process. V-ets, the founding member of the ETS oncogene family, was originally identified as part of the fusion oncogene encoded by the avian acute leukemia virus E26 and subsequent analysis of virus induced leukemias led to the initial isolation of two other members of the ETS gene family. PU.1 was identified as a target of insertional activation in the majority of tumors induced by the murine Spleen Focus Forming virus (SFFV), while fli-1 proved to be the target of Friend murine leukemia virus (F-MuLV) in F-MuLV induced erythroleukemia, as well as that of the 10A1 and Graffi viruses. The common features of the erythroid and myeloid diseases induced by these viruses provided the initial demonstration that these and other members of the ETS family play important roles in hematopoietic development as well as disease. This review provides an overview of the role of ETS genes in retrovirally induced neoplasia, their possible mechanisms of action, and how these viral studies relate to current knowledge of the functions of these genes in hematopoiesis.

Transformation by v-Myb.

The v-myb oncogene of the avian myeloblastosis virus (AMV) is unique among known oncogenes in that it causes only acute leukemia in animals and transforms only hematopoietic cells in culture. AMV was discovered in the 1930s as a virus that caused a disease in chickens that is similar to acute myelogenous leukemia in humans (Hall et al., 1941). This avian retrovirus played an important role in the history of cancer research for two reasons. First, AMV was used to demonstrate that all oncogenic viruses did not contain a single cancer-causing principle. In particular, although both Rous sarcoma virus (RSV) and AMV could replicate in cultures of either embryonic fibroblasts or hematopoietic cells, RSV could transform only fibroblasts whereas AMV could transform only hematopoietic cells (Baluda, 1963; Durban and Boettiger, 1981a). Second, chickens infected with AMV develop remarkably high white counts and therefore their peripheral blood contains remarkably large quantities of viral particles (Beard, 1963). For this reason AMV was often used as a prototypic retrovirus in order to study viral assembly and later to produce large amounts of reverse transcriptase for both research and commercial purposes. Following the discovery of the v-src oncogene of RSV and the demonstration that it arose from the normal c-src proto-oncogene, a number of acute leukemia viruses were analysed by similar techniques and found to also contain viral oncogenes of cellular origin (Roussel et al., 1979). In the case of AMV, it was shown that almost the entire retroviral env gene had been replaced by a sequence of cellular origin (initially called mab or amv, but later renamed v-myb) (Duesberg et al., 1980; Souza et al., 1980). Remarkably, sequences contained in this myb oncogene were shared between AMV and the avian E26 leukemia virus, but were not contained in any other acutely transforming retroviruses. In addition, the E26 virus contained a second sequence of cellular origin (ets) that was unique. The E26 leukemia virus was first described in the 1960s and causes an acute erythroblastosis in chickens, more reminiscent of the disease caused by avian erythroblastosis virus (AEV) than by AMV (Ivanov et al., 1962).

Excision of Ets by an inducible site-specific recombinase causes differentiation of Myb–Ets-transformed hematopoietic progenitors

Background: The Myb–Ets protein encoded by the E26 acute avian leukemia virus is a paradigm for the function of fused transcriptional activator oncoproteins. Myb–Ets transforms hematopoietic progenitor cells (Myb–Ets progenitors, MEPs) that can be induced to differentiate into eosinophilic and myeloid cells by the activation of pathways involving Ras and/or protein kinase C. The Ets portion of the fusion protein seems to be required to maintain the multipotency of MEPs: MEPs transformed with a temperature-sensitive E26 mutant with a lesion in Ets (ts1.1) and shifted to the non-permissive temperature predominantly form erythroid cells, but also form eosinophilic and myeloid cells. This interpretation is complicated, however, by the observation that ts1.1-transformed MEPs differ from MEPs transformed with wild-type E26 in that they express erythroid and eosinophil markers even at the permissive temperature.Results In order to alleviate the problems associated with the use of temperature-sensitive mutants we have designed a vector that allows the inducible deletion of the Ets domain. To this end, we introduced FLP recombinase target sites into the E26 virus on the 5′ and 3′ sides of ets and included within the same retroviral vector sequences encoding an estrogen-dependent FLP recombinase. This construct, termed FRV-3, is capable of transforming cells to produce a phenotype indistinguishable from that of MEPs obtained with wild-type virus. Hormone treatment of MEPs transformed with FRV-3 induced erythroid differentiation in a subpopulation of the cells; this subpopulation was found to have completely excised ets. However, in contrast to previous results obtained with ts1.1-transformed MEPs, no differentiation along the eosinophilic and myeloid lineages was seen in hormone-treated FRV-3-transformed MEPs.Conclusion Our results demonstrate the feasibility of using a site-specific recombinase to excise a fused oncoprotein domain encoded by a retrovirus. More specifically, they show that the Ets portion of the Myb–Ets protein selectively inhibits differentiation of MEPs along the erythroid lineage, and suggest that Ets is also required for their differentiation along the eosinophil and, possibly, myeloid lineages.