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S M Luger

Publications and source records attributed to S M Luger.

At least 19 recordsLinked to original sources
PubMed2006

Prognostic value of FDG-PET scan imaging in lymphoma patients undergoing autologous stem cell transplantation.

We conducted a retrospective analysis of 50 lymphoma patients (Hodgkin's disease and non-Hodgkin's lymphoma) who had an 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET) scan after at least two cycles of salvage chemotherapy and before autologous stem cell transplantation (ASCT) at our institution. The patients were categorized into FDG-PET negative (N = 32) and positive (N = 18) groups. The median follow-up after ASCT was 19 months (range: 3-59). In the FDG-PET-negative group, the median progression-free survival (PFS) was 19 months (range: 2-59) with 15 (54%) patients without progression at 12 months after ASCT. The median overall survival (OS) for this group was not reached. In the FDG-PET-positive group, the median PFS was 5 months (range: 1-19) with only one (7%) patient without progression at 12 months after ASCT. The median OS was 19 months (range: 1-34). In the FDG-PET-negative group, chemotherapy-resistant patients by CT-based criteria had a comparable outcome to those with chemotherapy-sensitive disease. A positive FDG-PET scan after salvage chemotherapy and prior ASCT indicates an extremely poor chance of durable response after ASCT.

Adult↗
PubMed2006

Autologous stem cell transplant in ALL: who should we be transplanting in first remission?

Long-term disease-free survival (DFS) has been reported after autologous stem cell transplantation for acute lymphoblastic leukemia. Phase II studies have evaluated its role in first and subsequent complete remission (CR) with DFS rates of up to 50%. It has been under-utilized in 1st CR in part, due to a concern that patients who relapse after autologous stem cell transplantation (ASCT) have fewer options for salvage treatment of relapsed disease. Unfortunately, survival rates of <5% are reported in patients who relapse, regardless of initial therapy. Few prospective, randomized trials have analyzed large enough numbers of patients to allow us to determine the appropriate patient population for autologous transplantation. Although variability in the available studies makes it difficult to draw a definite conclusion, and many issues remain unresolved, available data suggests that there may be a group of patients for whom ASCT in first remission is a reasonable and perhaps superior treatment choice. Factors such as risk features at diagnosis, and minimal residual disease following induction therapy greatly affect outcome following ASCT. The available data as well as the questions that remain to be answered will be discussed and reviewed.

Bone Marrow Purging↗
PubMed2005

Intensive graft-versus-host disease prophylaxis is required after unrelated-donor nonmyeloablative stem cell transplantation.

Nonmyeloablative stem cell transplantation (NST) harnesses the graft-versus-tumor effect while minimizing regimen-related toxicity, and can result in donor chimerism and remission. Acute graft-versus-host disease (GVHD) and infections are major complications after sibling NST. Toxicity of unrelated-donor (UD) NST and the most appropriate GVHD prophylaxis in this setting remain poorly defined. We describe 25 patients who received UD-NST conditioned with fludarabine and cyclophosphamide. The first six patients received cyclosporine (Cs) and mycophenolate mofetil (MMF) (n=5) or methotrexate (MTX) (n=1) as GVHD prophylaxis (group 1) and all developed grade III-IV acute GVHD. The next 19 patients received the same conditioning regimen with the addition of alemtuzumab, and all received Cs/MTX post-transplant. Engraftment and donor chimerism were achieved in all but one evaluable patient. In all, 15 patients died: five of six deaths in group 1 were attributable to acute GVHD, while deaths in group 2 were due to infection or progressive disease (P=0.05). The combination of Cs/MMF is inadequate GVHD prophylaxis for UD-NST. The use of Cs, MTX, and alemtuzumab eliminated severe acute GVHD; its impact on response merits further study.

Adult↗
PubMed2005

Long-term event-free survivors after high-dose therapy and autologous stem-cell transplantation for low-grade follicular lymphoma.

Although follicular lymphoma (FL) is generally responsive to conventional-dose chemotherapy, improved survival in patients with this disease has been difficult to demonstrate. High-dose chemo/radiotherapy followed by autologous stem-cell transplantation (ASCT) can improve response rates, although its effects on survival remain controversial. Between 1990 and 2003, we transplanted 49 patients with low-grade FL at our institution. Twenty-two patients (45%) had undergone histologic transformation at the time of ASCT. In all, 44 patients (90%) had relapsed disease and five patients (10%) were resistant to chemotherapy at the time of transplantation. After ASCT, 30 patients (61%) were in complete remission (CR). The median overall survival (OS) has not been reached, while the median event-free survival (EFS) is 2.4 years. At a median follow-up of 5.5 years (longest 12.4 years), a plateau has been reached with 56% of patients remaining alive, and 35% event-free. ASCT was well tolerated except for two (4%) treatment-related deaths. In multivariable analysis, CR after ASCT and age less than 60 years are the best predictors of EFS and OS. ASCT is thus a safe therapeutic approach in FL, resulting in long-term EFS and OS for some patients, even with transformed disease.

Adult↗
PubMed2002

Nonmyeloablative allogeneic stem cell transplantation for refractory Hodgkin's lymphoma complicated by interleukin-2 responsive progressive multifocal leukoencephalopathy.

Nonmyeloablative allogeneic stem cell transplantation (NMASCT) can be used to exploit the graft-versus-tumor (GVT) potential of allogeneic donor cells in the setting of reduced conditioning regimen toxicity. This approach is particularly attractive for patients who have received extensive prior therapy and are poor candidates for traditional allogeneic stem cell transplantation. However, toxicity in heavily pretreated patients remains uncertain. Additional immunosuppression in already immunocompromised patients may result in unexpected toxicity. We report a case of probable progressive multifocal leukoencephalopathy (PML) responsive to interleukin-2 (IL-2) following a NMASCT in a 29-year-old woman with relapsed Hodgkin's lymphoma. The patient developed severe neurological symptoms approximately 6 weeks following NMASCT associated with low CD4+ cell counts and magnetic resonance imaging (MRI) was consistent with PML. IL-2 therapy resulted in increasing CD4+ counts and progressive resolution of neurological symptoms. Disruption of IL-2 therapy led to neurological deterioration, which responded to reinstitution of IL-2 therapy. The patient's lymphoma initially progressed following NMASCT, but has responded to donor leukocyte infusions (DLI). This case reiterates the potent GVT potential of NMASCT in patients with Hodgkin's disease. However, it demonstrates the potential for severe complications related to immunosuppression, especially in heavily pretreated patients. The toxicity after NMASCT should not be understated and will need to be explored further.

Adult↗
PubMed2002

Gemtuzumab ozogamicin (Mylotarg) monotherapy for relapsed AML after hematopoietic stem cell transplant: efficacy and incidence of hepatic veno-occlusive disease.

Gemtuzumab ozogamicin (GO) (Mylotarg, CMA-676) is a novel chemotherapeutic agent consisting of an anti-CD33 monoclonal antibody linked to calicheamicin, and is associated with a 30% response rate in patients with CD33-positive acute myeloid leukemia (AML) in first relapse. GO therapy has a 20% incidence of grade 3 or 4 hepatotoxicity, and has recently been associated with hepatic veno-occlusive disease (VOD). The efficacy and toxicity of GO in patients with AML who have relapsed after hematopoietic stem cell transplant (HSCT) is unknown, as this population was largely excluded from phase II studies. We reviewed the outcomes of eight consecutive patients with AML who received GO following relapse after HSCT. Two (25%) had responses to GO. One patient, who had had two previous HSCT and prior hyperbilirubinemia, developed severe VOD and died 14 days after GO therapy. The other seven patients did not meet diagnostic criteria for VOD. We conclude that GO can be safe and effective in patients who relapse following HSCT, but that caution is warranted in patients with multiple risk factors for VOD.

Acute Disease↗
PubMed2001

Nuclear factor-kappaB is constitutively activated in primitive human acute myelogenous leukemia cells.

Human acute myelogenous leukemia (AML) is thought to arise from a rare population of malignant stem cells. Cells of this nature, herein referred to as leukemic stem cells (LSCs), have been documented for nearly all AML subtypes and appear to fulfill the criteria for stem cells in that they are self-renewing and give rise to the cells found in many leukemic populations. Because these cells are likely to be critical for the genesis and perpetuation of leukemic disease, the present studies sought to characterize unique molecular properties of the LSC population, with particular emphasis on the transcription factor, nuclear factor-kappaB (NF-kappaB). Previous experiments have shown that unstimulated human CD34(+) progenitor cells do not express NF-kappaB. In contrast, primary AML CD34(+) cells display readily detectable NF-kappaB activity as assessed by electrophoretic mobility shift assay and gene expression studies. Furthermore, detailed analyses of enriched AML stem cells (CD34(+)/CD38(-)/CD123(+)) indicate that NF-kappaB is also active in the LSC population. Given the expression of NF-kappaB in leukemic, but not normal primitive cells, the hypothesis that inhibition of NF-kappaB might induce leukemia-specific apoptosis was tested by treating primary cells with the proteasome inhibitor MG-132, a well-known inhibitor of NF-kappaB. Leukemic CD34(+)/CD38(-) cells displayed a rapid induction of cell death in response to MG-132, whereas normal CD34(+)/CD38(-) cells showed little if any effect. Taken together, these data indicate that primitive AML cells aberrantly express NF-kappaB and that the presence of this factor may provide unique opportunities to preferentially ablate LSCs.

Actins↗
PubMed2001

Sudden death among patients with acute promyelocytic leukemia treated with arsenic trioxide.

Arsenic trioxide has been shown to be effective in treating acute promyelocytic leukemia (APL), with minimal overall toxicity reported to date. A phase I/II study was initiated in June 1998 using arsenic trioxide for relapsed APL to determine the maximum tolerated or minimal effective dose and to determine the efficacy of treatment at that dose. Ten patients received 1 to 4 monthly cycles of treatment with 0.1 mg/kg per day intravenous arsenic trioxide. Six of 7 patients evaluable for response achieved cytogenetic or molecular complete remission. However, 3 patients died suddenly during the first cycle of treatment. Autopsies obtained on 2 of these failed to identify a cause of sudden death, despite evidence of pulmonary hemorrhage in one. A third patient, for whom an autopsy was not performed, became asystolic and died while on continuous cardiac telemetry. These observations suggest that arsenic trioxide may be significantly or even fatally toxic at doses currently used and that caution is warranted in its use.

Adult↗
PubMed2001

Expression of tumor-suppressor genes interferon regulatory factor 1 and death-associated protein kinase in primitive acute myelogenous leukemia cells.

Previous studies indicate that human acute myelogenous leukemia (AML) arises from a rare population of leukemic stem cells. Cells of this nature can initiate and maintain leukemic cell growth in both long-term cultures and nonobese diabetic/severe combined immune-deficient mice. To characterize the biology of primitive AML cells, gene expression screens were performed with 7 primary AML and 3 normal specimens. For each sample, stem cell populations (CD34(+)/CD38(-)) were isolated and used to synthesize radiolabeled complementary DNA (cDNA). AML vs normal probes were then hybridized to cDNA arrays containing genes related to cancer and apoptosis. Of approximately 1400 genes analyzed, 2 tumor-suppressor genes were identified that were overexpressed in all 7 of the AML CD34(+)/CD38(-) cell populations: death-associated protein kinase and interferon regulatory factor 1. Expression of each gene was confirmed by reverse-transcription polymerase chain reaction and immunoblot analysis. It is proposed that tumor-suppressor proteins play a role in the biology of primitive AML cells. (Blood. 2001;97:2177-2179)

ADP-ribosyl Cyclase↗
PubMed2001

Allogeneic cell therapy for patients who relapse after autologous stem cell transplantation.

Allogeneic donor leukocytes can be used after nonmyeloablative conditioning to exploit their graft-versus-tumor (GVT) activity in the setting of reduced conditioning-regimen toxicity. This approach may be particularly useful for patients who relapse after autologous stem cell transplantation (SCT). However, GVT activity, toxicity, and ability to establish mixed chimerism may differ in patients who were heavily pretreated prior to SCT compared with patients treated earlier in the course of their disease. We have performed a series of studies of nonmyeloablative allogeneic transplantation and present data on the subset of 14 patients treated for relapse after autologous SCT: 4 patients received no conditioning and unstimulated donor leukocyte infusions (DLI), 10 patients received conditioning with fludarabine and cyclophosphamide followed by unstimulated or granulocyte-colony-stimulating factor (G-CSF)-stimulated allogeneic peripheral blood stem cells (PBSCs), 4 patients received no graft-versus-host disease (GVHD) prophylaxis, and 10 patients received cyclosporine GVHD prophylaxis. All but 1 patient had sustained donor chimerism at least 30 days after allogeneic cell therapy (ACT), and 8 patients had more than 80% donor chimerism after ACT. Acute GVHD developed in 11 patients (grade III-IV, n = 6). Aplasia was more frequent in the patients receiving unstimulated PBSCs, despite the development of mixed chimerism. There were 6 complete responses and 4 partial responses; response was independent of conditioning and growth-factor stimulation of the donor graft. Five patients died of treatment-related causes and 4 patients died from progressive disease. Four patients remained alive 27 to 194 weeks (median, 66 weeks) after ACT. Prior autologous SCT may define a subset of patients at particularly high risk for GVHD and other toxicity after ACT. However, these data show that ACT with either DLI or G-CSF-stimulated blood cells results in direct GVT activity in some patients with Hodgkin's disease, myeloma, and non-Hodgkin's lymphoma, even after relapse from autologous SCT. Most patients developed donor chimerism with minimal conditioning. Alternative prophylactic regimens that control GVHD while maintaining GVT are needed to improve outcomes in these heavily pretreated patients.

Adolescent↗
PubMed2000

Effect of postremission chemotherapy before human leukocyte antigen-identical sibling transplantation for acute myelogenous leukemia in first complete remission.

Allogeneic bone marrow transplantation is an effective postremission strategy for patients with acute myelogenous leukemia (AML) in first complete remission (CR). The value of administering consolidation chemotherapy before human leukocyte antigen (HLA)-identical sibling transplantation is not established. Outcomes of patients with AML in first CR receiving no consolidation therapy, standard-dose cytarabine consolidation therapy, and high-dose cytarabine consolidation therapy before HLA-identical sibling transplantation were compared. Five-year treatment-related mortality rates were 30% (95% confidence interval [CI], 18% to 42%) in patients receiving no consolidation chemotherapy, 22% (95% CI, 17% to 28%) in those receiving standard-dose cytarabine consolidation, and 24% (95% CI, 17% to 31%) in those receiving high-dose cytarabine (P = NS). Five-year cumulative incidences of relapse were 19% (10% to 30%), 21% (16% to 27%), and 17% (11% to 24%), respectively (P = NS). Five-year probabilities of leukemia-free survival were 50% (36% to 63%), 56% (49% to 63%), and 59% (50% to 66%), respectively (P = NS). Five-year probabilities of overall survival were 60% (46% to 71%), 56% (49% to 63%), and 60% (51% to 67%), respectively (P = NS). The data indicate that postremission consolidation with cytarabine before allogeneic transplantation for AML in first CR is not associated with improved outcome compared to proceeding directly to transplantation after successful induction. (Blood. 2000;96:1254-1258)

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

The interleukin-3 receptor alpha chain is a unique marker for human acute myelogenous leukemia stem cells.

Recent studies suggest that the population of malignant cells found in human acute myelogenous leukemia (AML) arises from a rare population of leukemic stem cells (LSCs). LSCs have been documented for nearly all AML subtypes and have been phenotypically described as CD34+/CD38- or CD34+/HLA-DR-. Given the potentially critical role of these primitive cells in perpetuating leukemic disease, we sought to further investigate their molecular and cellular characteristics. Flow cytometric studies using primary AML tissue showed that the interleukin-3 receptor alpha chain (IL-3Ralpha or CD123) was strongly expressed in CD34+/CD38- cells (98 +/- 2% positive) from 16 of 18 primary specimens. Conversely, normal bone marrow derived CD34+/CD38- cells showed virtually no detectable expression of the CD123 antigen. To assess the functional role of IL-3Ralpha positive cells, purified CD34+/CD123+ leukemia cells were transplanted into immune deficient NOD/SCID mice. These experiments showed that CD123+ cells were competent to establish and maintain leukemic populations in vivo. To begin to elucidate a biological role for CD123 in leukemia, primary AML samples were analyzed with respect to signal transduction activity in the MAPK, Akt, and Stat5 pathways. Phosphorylation was not detected in response to IL-3 stimulation, thereby suggesting CD123 is not active in conventional IL-3-mediated signaling. Collectively, these data indicate that CD123 represents a unique marker for primitive leukemic stem cells. Given the strong expression of this receptor on LSCs, we propose that targeting of CD123 may be a promising strategy for the preferential ablation of AML cells.

Animals↗
PubMed1999

Stem cell transplantation for metastatic breast cancer: analysis of tumor contamination.

The purpose of this study was to determine the efficacy, engraftment kinetics, effect of bone marrow tumor contamination, and safety of high-dose therapy and granulocyte-colony stimulating factor (G-CSF) mobilized peripheral blood progenitor cell (PBPC) support for patients with responding metastatic breast cancer. Forty two patients underwent G-CSF (10 microg/kg) stimulated PBPC harvest. PBPC and bone marrow aspirates were analyzed by histologic and immunocytochemical methods for tumor contamination. Thirty-seven patients received high-dose therapy consisting of cyclophosphamide 6 g/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) given as an infusion over 4 d followed by PBPC reinfusion and G-CSF (5 microg/kg) support. No transplant related deaths or grade 4 toxicity was recorded. CD34+ cells/kg infused was predictive of neutrophil and platelet recovery. With a median follow-up of 38 months, three year survival was 44% with relapse-free survival of 19%. Histological bone marrow involvement, found in 10 patients, was a negative prognostic factor and was associated with a median relapse-free survival of 3.5 months. Tumor contamination of PBPC by immunohistochemical staining was present in 22.5% of patients and found not to be correlated with decreased survival. G-CSF stimulated PBPC collection followed by a single course of high dose chemotherapy and stem cell infusion with G-CSF stimulated marrow recovery leads to rapid, reliable engraftment with low toxicity and promising outcome in women with responding metastatic breast cancer.

Adult↗
PubMed1999

Autologous stem-cell transplant after conventional dose adjuvant chemotherapy for high-risk breast cancer: impact on the delivery of local-regional radiation therapy.

BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation is used increasingly in the treatment of poor-prognosis primary breast cancer. Because these patients may be cured with standard multimodality therapy, it is important to address both the efficacy of transplantation, and its effect on the delivery of standard treatments including local radiation therapy. PATIENTS AND METHODS: Patients with high risk primary breast cancer were treated with high-dose cyclophosphamide and thiotepa and stem-cell transplant following surgery and conventional-dose adjuvant chemotherapy. Outcome, including sites of failure and delivery of local radiation therapy, was assessed for 103 patients. RESULTS: Overall and disease-free survival rates at 18 months were 83% (+/- 4%) and 77% (+/- 4%) respectively. Twenty patients (19.4%) received radiation therapy prior to transplant. Of the remaining 83, 77 received radiation therapy after transplant. Overall, 5 (19.2%) of 26 first sites of recurrence were local alone. For patients receiving radiation prior to transplant, 3 of 7 (43%, 95% CI: 6%-80%) sites of first recurrence were local, while 2 of 19 (10.5%, 95% CI: 0%-24.5%) sites of first recurrence were local alone in patients receiving post-transplant radiation or no radiation. CONCLUSION: Transplantation does not appear to significantly compromise the delivery or outcome of local radiation therapy for primary breast cancer.

Adult↗
PubMed1997

Cycles of dose-intensive chemotherapy with peripheral stem cell support in persistent or recurrent platinum-sensitive ovarian cancer.

OBJECTIVE: The objective was to determine the toxicity and surgically documented response rate of sequential high-dose chemotherapy with peripheral stem cell support in patients with persistent or recurrent cisplatin-sensitive ovarian cancer. METHODS: Fourteen patients (average age, 45 years) were treated with cyclophosphamide (4.5 g/m2), followed by granulocyte colony-stimulating factor (G-CSF)-stimulated peripheral stem cell harvests. The subsequent regimen prescribed three courses of carboplatin (1 g/m2) and cyclophosphamide (1.5 g/m2 with 2-mercaptoethanesulfonate) every 2 weeks with stem cell support. This was followed by three courses of paclitaxel at 250 mg/m2 every 2 weeks with G-CSF support only. Six patients were entered on the basis of a positive second-look laparotomy and 8 patients had a first recurrence after at least a 6-month disease-free interval. RESULTS: Fourteen patients were entered and 12 patients completed all planned courses of therapy (mean time, 13 weeks). Normal hematopoiesis was reestablished after each cycle. Hospitalization for neutropenic fever occurred in 11/93 cycles (11.8%). Thirteen patients required blood transfusions and in 12 patients platelet transfusions were given. One patient had grade 3 neurotoxicity. An initial elevated CA 125 returned to normal in 7/8 patients (88%) and 71% of patients with measurable disease responded to therapy. There were 2 pathologic complete responders (PCR), making the PCR rate 2/14 or 14% (0-35%). CONCLUSION: Although this regimen was well tolerated and clinical response rates were high, the surgically documented response rate was not clearly superior to conventional salvage regimens in platinum-sensitive patients.

Adult↗
PubMed1996

A functional analysis of protooncogene Vav's role in adult human hematopoiesis.

The Vav protooncogene is expressed almost exclusively in hematopoietic cells, but its role in regulating adult human hematopoietic cell development remains uncertain. To analyze Vav function in adult blood cell formation, we used antisense (AS) oligodeoxynucleotides (ODN) to disrupt its expression in normal and malignant human hematopoietic cells. Bone marrow or peripheral blood mononuclear cells (MNC) were obtained from consenting normal donors and patients with acute or chronic myelogenous leukemia (AML and CML, respectively) and polycythemia vera (PV). Adherent and T-cell-depleted (A-T-) MNC or CD34+ MNC were exposed to unmodified sense, antisense, or scrambled sequence ODN corresponding to codons 2-7 of Vav's mRNA sequence. Cells were then assayed for Vav mRNA expression by reverse transcription-polymerase chain reaction and Vav protein expression by Western binding. After showing that Vav-targeted AS ODN could specifically diminish Vav mRNA and protein expression, we assessed the ability of Vav-deficient cells to form myeloid and erythroid colonies in methyl-cellulose cultures. When normal CD34+ MNC were exposed to Vav AS ODN, no effect on colony-forming unit-granulocyte-macrophage (CFU-GM) or CFU-megakaryocyte colony formation was observed. In contrast erythroid colony growth was inhibited by a mean +/- SD of 62% +/- 16%. In patients with hematopoietic malignancies. Vav-targeted AS ODN inhibited CFU-GM colony formation in a sequence-specific and dose-dependent manner in 1 of 3 AML, 13 of 17 CML, and 2 of 2 PV patients. At the highest concentration used, the Vav AS ODN inhibited CFU-GM colony formation from 66% to 81% when compared with control cell colony growth. Burst-forming unit-erythroid (BFU-E) colony-formation was also assessed in 7 PV patients. The Vav-targeted AS ODN inhibited BFU-E colony formation in all by a mean +/- SD of 81% +/- 4%. These findings suggest that Vav function may not be easily complemented in a significant subset of normal adult erythroid progenitor cells and may also be necessary for myeloid progenitor cell growth in a variety of hematopoietic malignancies.

Adult↗
PubMed1995

Vav is necessary for prolactin-stimulated proliferation and is translocated into the nucleus of a T-cell line.

Stimulation of the prolactin receptor (PRLr) with ligand activates multiple kinase cascades. The proximal mediators involved in the activation of the PRL-activated Raf-1 cascade in T-cells, however, remain poorly characterized. The role of one proximal signaling protein, namely p95vav, during PRLr signal transduction was examined in the Nb2 T-cell line. The novel results obtained here indicate that Vav is transiently associated with the PRLr and is necessary for PRL-stimulated proliferation. During PRL stimulation, a rapid and dramatic increase in guanine nucleotide exchange factor (GEF) activity was found to be associated with Vav immunoprecipitates. Concomitantly, an increase in Vav phosphorylation on serine-threonine residues was observed. The Vav-associated GEF activation could be inhibited by staurosporine and calphostin, but not herbimycin, suggesting a modulatory role for phosphorylation at serine-threonine residues. Treatment of Nb2 cells with antisense Vav oligonucleotide ablated Vav expression and blocked PRL-driven proliferation, but failed to inhibit PRL-induced GEF activation within Nb2 lysates. These data indicate that GEF activity may not be intrinsic to Vav as has been previously suggested, but either resides in or is complemented by an associated GEF. Subsequent to the transient activation of associated GEF activity, Vav was found to translocate into the Nb2 cell nucleus. Thus, Vav may utilize two independent mechanisms in T-cells, namely the activation of an associated GEF and direct nuclear internalization, to mediate PRLr signaling.

Animals↗