Vanishing bile duct syndrome after allogeneic bone marrow transplantation: is it the end of the road?

Posted by rob on August 16, 2014 under Uncategorized | Comments are off for this article

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Vanishing bile duct syndrome after allogeneic bone marrow transplantation: is it the end of the road?

Turk J Gastroenterol. 2013;24(4):359-62

Authors: Bakanay ?M, Bilgin AU, Bekta? M, Idilman R, Erden E, Arat M, Arslan Ö

Abstract

In this paper, we report the case of a 19-year-old male patient who presented with lymphoblastic phase of chronic myeloid leukemia and received an allogeneic bone marrow transplant from his cousin. The patient experienced severe, steroid-refractory acute graft versus-host disease of skin, gastrointestinal tract and liver that required further immunosuppression. However, hepatic graft-versus-host disease was complicated with vanishing bile duct syndrome, characterized by progressive destruction of small intrahepatic bile ducts, which was refractory to all available therapies and eventually led to end-stage liver disease. The pathogenesis and treatment of graft-versus-host disease after allogeneic hematopoietic cell transplantation is discussed with an emphasis on liver transplantation for intractable hepatic graft-versus-host disease.

PMID: 24254270 [PubMed - indexed for MEDLINE]

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Evaluation of clinical performance of the major BCR-ABL mRNA detection kit which enables conversion to international standard scale using the reference material calibrator.

Posted by rob on August 13, 2014 under Uncategorized | Comments are off for this article

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Evaluation of clinical performance of the major BCR-ABL mRNA detection kit which enables conversion to international standard scale using the reference material calibrator.

Rinsho Ketsueki. 2014 May;55(5):534-40

Authors: Miyamura K, Okamoto S, Usui N, Hino M, Akashi K, Nakaseko T, Takahashi N, Nakatani K, Takahashi K, Nobori T, Naoe T

Abstract

In a multicenter study, we evaluated the Major BCR-ABL mRNA/ABL mRNA quantification kit (M135R), which uses reference material included in the kit designed to report results using the international scale (IS). In total, 127 samples were studied. A good correlation was observed between M135R results and home-brew RT-qPCR results, which are reported on the IS using a conversion factor (r=0.90; n=115). However, the correlation coefficient between M135R results and Amp-CML results was relatively low (r=0.56; n=108). A good correlation was observed between M135R results from the two assay sites (r=0.94; n=115). The subset analysis of samples from the two assay sites showed M135R to have a good correlation even in the low IS range (r=0.98; IS?1%). M135R showed high sensitivity and accuracy for detecting minimal residual disease and is considered to be a useful tool for treatment response assessment and for early detection of recurrence in CML patients.

PMID: 24881918 [PubMed - indexed for MEDLINE]

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Management of chronic myeloid leukemia for Japanese patients in the era of TKIs.

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Management of chronic myeloid leukemia for Japanese patients in the era of TKIs.

Rinsho Ketsueki. 2014 May;55(5):497-507

Authors: Usui N

PMID: 24881914 [PubMed - indexed for MEDLINE]

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Predictive factors of successful treatment-free remission for patients with chronic myeloid leukemia.

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Predictive factors of successful treatment-free remission for patients with chronic myeloid leukemia.

Rinsho Ketsueki. 2014 May;55(5):489-96

Authors: Takahashi N

PMID: 24881913 [PubMed - indexed for MEDLINE]

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Monocytic crisis of chronic myeloid leukemia in the era of tyrosine kinase inhibitor.

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Monocytic crisis of chronic myeloid leukemia in the era of tyrosine kinase inhibitor.

J Clin Exp Hematop. 2013;53(3):227-33

Authors: Tsunemine H, Arima H, Itoh K, Sakane-Ishikawa E, Akasaka H, Kodaka T, Takahashi T

Abstract

A 47-year-old man was diagnosed with Philadelphia chromosome-positive chronic myeloid leukemia (CML) in October 2005. He could not receive treatment with imatinib mesylate due to his economic circumstances. He was consequently treated with hydroxyurea with partial hematological remission until June 2008. Although imatinib mesylate was started thereafter, the adherence to this treatment was poor because of his occupational circumstances. In September 2009, imatinib mesylate was switched to nilotinib, with a subsequent phase of acceleration of the disease, presumably due to his poor adherence to the treatment. Dasatinib was started in September 2010, with transient hematological response and final blastic crisis of the disease in January 2011, regardless of improved adherence. Blast cells showed immature monocytic morphology and were positive for ?-naphtylbutyrate esterase staining. They also expressed surface CD14 and CD64 antigens. A diagnosis of rare monocytic crisis of CML was made. He was treated with low-dose nilotinib following cytoreduction with MEC (mitoxantrone, etoposide, and cytarabine) chemotherapy. Severe leucopenia without circulating leukemic cells continued for about 2 months with sustained hepatosplenomegaly, and he died of pneumonia in March 2012. Necropsy showed severe bone marrow hypoplasia with focal infiltration of mature leukemic cells and similar infiltration in the liver.

PMID: 24369225 [PubMed - indexed for MEDLINE]

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A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib.

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A single nucleotide polymorphism in cBIM is associated with a slower achievement of major molecular response in chronic myeloid leukaemia treated with imatinib.

PLoS One. 2013;8(11):e78582

Authors: Augis V, Airiau K, Josselin M, Turcq B, Mahon FX, Belloc F

Abstract

PURPOSE: BIM is essential for the response to tyrosine-kinase inhibitors (TKI) in chronic myeloid leukaemia (CML) patients. Recently, a deletion polymorphism in intron 2 of the BIM gene was demonstrated to confer an intrinsic TKI resistance in Asian patients. The present study aimed at identifying mutations in the BIM sequence that could lead to imatinib resistance independently of BCR-ABL mutations.

EXPERIMENTAL DESIGN: BIM coding sequence analysis was performed in 72 imatinib-treated CML patients from a French population of our centre and in 29 healthy controls (reference population) as a case-control study. Real-time quantitative PCR (RT qPCR) was performed to assess Bim expression in our reference population.

RESULTS: No mutation with amino-acid change was found in the BIM coding sequence. However, we observed a silent single nucleotide polymorphism (SNP) c465C>T (rs724710). A strong statistical link was found between the presence of the T allele and the high Sokal risk group (p?=?0.0065). T allele frequency was higher in non responsive patients than in the reference population (p?=?0.0049). Similarly, this T allele was associated with the mutation frequency on the tyrosine kinase domain of BCR-ABL (p<0.001) and the presence of the T allele significantly lengthened the time to achieve a major molecular response (MMR). Finally, the presence of the T allele was related to a decreased basal expression of the Bim mRNA in the circulating mononuclear cells of healthy controls.

CONCLUSION: These results suggest that the analysis of the c465C>T SNP of BIM could be useful for predicting the outcome of imatinib-treated CML patients.

PMID: 24223824 [PubMed - indexed for MEDLINE]

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Germination of spores of certain Clostridium species in the presence of penicillin.

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Germination of spores of certain Clostridium species in the presence of penicillin.

Antibiot Chemother (Northfield Ill). 1951 Jun;1(3):198-202

Authors: WYNNE ES, HARRELL K

PMID: 24541114 [PubMed - indexed for MEDLINE]

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[Prolonged urethane therapy of chronic myeloid leukemia].

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[Prolonged urethane therapy of chronic myeloid leukemia].

Arch Inn Med. 1951 Mar;1(6):692-8

Authors: BAUR E

PMID: 24540628 [PubMed - indexed for MEDLINE]

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[Not Available].

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[Not Available].

Rev Esp Pediatr. 1948 Mar-Apr;4(2):172-83

Authors: AVIGNON M

PMID: 18876587 [PubMed - indexed for MEDLINE]

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[Not Available].

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[Not Available].

Sang. 1947;18(4):234-42

Authors: BERNARD J, MASSE NP

PMID: 20257367 [PubMed - indexed for MEDLINE]

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[Not Available].

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[Not Available].

Sang. 1947;18(7):418-20

Authors: RAYNARD R, IMBERT C, D’ESHOUGUES JR

PMID: 18919857 [PubMed - indexed for MEDLINE]

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Nonmyeloablative Allogeneic Hematopoietic Stem-Cell Transplantation for GATA2 Deficiency.

Posted by rob on August 12, 2014 under Uncategorized | Comments are off for this article

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Nonmyeloablative Allogeneic Hematopoietic Stem-Cell Transplantation for GATA2 Deficiency.

Biol Blood Marrow Transplant. 2014 Aug 8;

Authors: Grossman J, Cuellar-Rodriguez J, Gea-Banacloche J, Zerbe C, Calvo K, Hughes T, Hakim F, Cole K, Parta M, Freeman A, Holland SM, Hickstein DD

Abstract

We treated 14 patients with GATA2 deficiency using a nonmyeloablative allogeneic hematopoietic stem cell transplantation (HSCT) regimen. Four patients received peripheral blood stem cells (PBSC) from matched-related donors (MRD), four patients received PBSC from matched-unrelated donors (URD), four patients received HSC from umbilical cord blood donors (UCB), and two patients received bone marrow cells from haploidentical related donors. MRD and URD recipients received conditioning with three days of fludarabine and 200cGy total body irradiation (TBI). Haploidentical related donor recipients and UCB recipients received cyclophosphamide and two additional days of fludarabine along with the 200 cGY TBI. MRD, URD, and UCB recipients received tacrolimus and sirolimus for post-transplant immunosuppression, whereas haploidentical recipients received high-dose cyclophosphamide followed by tacrolimus and mycophenolate mofetil. Eight patients are alive with reconstitution of the severely deficient monocyte, B-cell, and Natural Killer (NK) cell populations and reversal of the clinical phenotype at a median follow-up of 3.5 years. Two patients rejected the donor graft (one URD and one UCB), and one MRD recipient relapsed with myelodysplastic syndrome (MDS) post-transplant. We are currently using a high-dose conditioning regimen with busulfan and fludarabine in patients with GATA2 deficiency to achieve more consistent engraftment and eradication of the malignant myeloid clones.

PMID: 25111582 [PubMed - as supplied by publisher]

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How I determine if and when to recommend stopping tyrosine kinase inhibitor treatment for chronic myeloid leukaemia.

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How I determine if and when to recommend stopping tyrosine kinase inhibitor treatment for chronic myeloid leukaemia.

Br J Haematol. 2014 Jul;166(1):3-11

Authors: Ross DM, Hughes TP

Abstract

Treatment-free remission (TFR) has recently emerged as a goal of treatment in chronic myeloid leukaemia (CML). Molecular remission is sustained in around 30% of imatinib-treated patients who stop treatment after ?2 years with undetectable minimal residual disease (UMRD) by conventional real-time reverse transcription polymerase chain reaction. An additional 20-30% of patients will lose UMRD, but remain in stable major molecular remission off treatment. Most patients with molecular recurrence have a significant increase in BCR-ABL1 within the first 6 months off treatment, but there are also rare late relapses. As re-treatment with imatinib restores control, a trial of TFR is safe so long as careful molecular monitoring is provided to enable prompt re-treatment. The minimum eligibility criteria for a trial of TFR are not yet defined, but the available data support a MRD level of around a molecular response of 4.5 log for at least 2 years. Factors associated with a higher probability of TFR include low risk Sokal score, prior interferon treatment, longer total duration of imatinib treatment and higher numbers of natural killer cells at the time of imatinib discontinuation. Preliminary data suggest that the rate of TFR in patients treated with more potent tyrosine kinase inhibitors will probably be higher. The biology that underlies TFR is an area of active investigation.

PMID: 24754670 [PubMed - indexed for MEDLINE]

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Tumour promoting functions of TGF-? in CML-initiating cells.

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Tumour promoting functions of TGF-? in CML-initiating cells.

J Biochem. 2012 Nov;152(5):383-5

Authors: Miyazono K

Abstract

Recent data have shown that transforming growth factor-? (TGF-?) plays bi-directional roles in the maintenance of cancer stem cells in a cell-type and context-dependent manner. Zhu et al. (TGF-?1-induced PI3K/Akt/NF-?B/MMP9 signalling pathway is activated in Philadelphia chromosome-positive chronic myeloid leukaemia hemangioblasts. J. Biochem. 2011;149:405-414) studied the functions of TGF-? in hemangioblasts from patients with chronic myeloid leukemia (CML), which displayed properties of leukemia-initiating cells. They have shown that the BCR/ABL oncoprotein induced the production of TGF-? in the CML hemangioblasts, and that TGF-? activated the phosphoinositide 3-kinase-Akt-NF-?B pathway in these cells. Activation of this pathway enhanced the production of matrix metalloproteinase-9 leading to increased synthesis of soluble Kit ligand and intercellular adhesion molecule-1. TGF-? is known to maintain the CML-initiating cells through the Akt-FoxO pathway. Together, these findings suggest that TGF-? may exhibit multiple functions in progression of CML through acting on leukemia-initiating cells.

PMID: 22989931 [PubMed - indexed for MEDLINE]

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The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell.

Posted by rob on August 8, 2014 under Uncategorized | Comments are off for this article

The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell.

Exp Hematol. 2014 Aug 4;

Authors: Shima T, Miyamoto T, Kikushige Y, Yuda J, Tochigi T, Yoshimoto G, Kato K, Takenaka K, Iwasaki H, Mizuno S, Goto N, Akashi K

Abstract

The cellular properties of leukemia stem cells (LSCs) are achieved at least through Class I and Class II mutations that generate signals for enhanced proliferation and impaired differentiation, respectively. Here we show that in t(8;21) acute myelogenous leukemia (AML), hematopoietic stem cells (HSCs) transform into LSCs via definitively-ordered acquisition of Class II (AML1/ETO) and then Class I (c-KIT mutant) abnormalities. Six t(8;21)AML patients with c-KIT mutants maintaining >3 years of complete remission were analyzed. At diagnosis, all single LSCs had both AML1/ETO and c-KIT mutations. However, in remission, 16 out of 1728 CD34(+)CD38(-) HSCs and 89 out of 7187 single HSC-derived myelo-erythroid colonies from these patients had AML1/ETO, whose breakpoints were identical to those found in LSCs. These cells had wild-type c-KIT, which expressed AML1/ETO at a low level, and could differentiate into mature blood cells, suggesting that they may be the persistent pre-leukemic stem cells. Microarray analysis suggested that mutated c-KIT signaling provides LSCs with enhanced survival and proliferation. Thus, in t(8;21)AML, the acquisition of AML1/ETO is not sufficient, and the subsequent upregulation of AML1/ETO and the additional c-KIT mutant signaling are critical steps for transformation into LSCs.

PMID: 25101977 [PubMed - as supplied by publisher]

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Multiple gastrointestinal stromal tumors during nilotinib treatment for chronic myelogenous leukemia in a patient with neurofibromatosis type 1.

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Multiple gastrointestinal stromal tumors during nilotinib treatment for chronic myelogenous leukemia in a patient with neurofibromatosis type 1.

Nihon Shokakibyo Gakkai Zasshi. 2014 Aug;111(8):1579-86

Authors: Shugo H, Hodo Y, Watanabe T, Uwafuji S, Sugimori J, Hayashi Y, Harada K, Nakanuma Y, Yoneshima M

Abstract

A 60-year-old woman with neurofibromatosis type 1 presented to our hospital with melena. She reported a 1-year history of treatment with nilotinib hydrochloride hydrate for chronic myelogenous leukemia. Contrast-enhanced abdominal computed tomography revealed multiple intestinal tumors that were subsequently diagnosed as gastrointestinal stromal tumors (GIST) using single-balloon enteroscopy. Although the tumors showed no significant change over 1 year, partial jejunal resection was performed to confirm the diagnosis. Immunohistochemically, the tumors were GIST.

PMID: 25100347 [PubMed - in process]

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Response monitoring, tolerability, and effectiveness of imatinib treatment for chronic myeloid leukemia in a retrospective research database.

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Response monitoring, tolerability, and effectiveness of imatinib treatment for chronic myeloid leukemia in a retrospective research database.

J Natl Compr Canc Netw. 2014 Aug;12(8):1113-21

Authors: Stenehjem DD, Albright F, Kuo KL, Raimundo K, Bauer H, Shami PJ, Deininger MW, Chen L, Brixner DI

Abstract

Retrospective review of imatinib monitoring through electronic health records (EHR) can provide valuable insight into the current management of chronic myelogenous leukemia (CML). This study retrospectively reviewed EHRs from 2001 to 2010 of patients with chronic phase CML (CP-CML) treated with first-line imatinib. Chart evaluations included a review of cytogenetic and molecular testing, overall survival, adverse drug events (ADEs), and therapy modifications. A total of 54 patients with CP-CML were treated with first-line imatinib and had either cytogenetic or molecular testing within 18 months of imatinib initiation. Within the first 18 months of treatment, 33 of 45 patients (73%) undergoing cytogenetic testing experienced a complete cytogenetic response (median, 241 days; range, 110-542 days) and 24 of 48 patients (50%) receiving molecular testing achieved at least a major molecular response (median, 253 days; range, 99-546 days). The average number of cytogenetic and molecular tests conducted within the first 18 months was 2.5 and 3.8, respectively. Nineteen of 54 (35%) had a dose increase of imatinib (>400 mg; median, 329 days; range, 21-1968 days). The 5-year estimated overall survival rate was 88.5%. Between 2006 and 2010 (n=30; 56%), 7 patients (23%) transitioned to dasatinib or nilotinib (median, 399 days from diagnosis; range, 180-1046 days) because of suboptimal response or treatment failure (n=5) and imatinib ADEs (n=2). Forty-six imatinib-associated ADEs occurred in 31 patients (57%), of which 10 (32%) received dose reductions (median, 52 days) and 6 (19%) had discontinuations (median, 139 days). Closely monitored patients with CML treated with imatinib at an NCCN Member Institution experienced outcomes comparable to those reported in key clinical trials.

PMID: 25099443 [PubMed - in process]

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Sweet’s syndrome.

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Sweet’s syndrome.

Indian J Dent Res. 2014 May-Jun;25(3):401-5

Authors: Limdiwala PG, Parikh SJ, Shah JS

Abstract

Acute febrile neutrophilic dermatosis or Sweet’s syndrome (SS) is characterized by painful, erythematous plaques of rapid onset accompanied by fever. The etiology of SS is unknown and it may be associated with antecedent infections, malignancies, autoimmune diseases, drugs and vaccines, upper respiratory or gastrointestinal infection, pregnancy, inflammatory bowel disease as well as chemotherapy or idiopathic. The standard therapy for SS is systemic corticosteroids. We report a rare case of 19-year-old young male patient with complaint of severe ill-defined type of pain in both jaws associated with plaques and papules on extensor surfaces of upper and lower extremities with bodyache and myalgia. Histopathological examination suggested perivascular neutrophilic infiltration with scattered eosinophils. Sweet syndrome has rare oral manifestations secondary to hematological changes. It can also present as a paraneoplastic syndrome (malignancy-associated form of condition, which is most commonly related to acute myelogenous leukemia), which leads to poor prognosis and thus it requires careful examination, early diagnosis and long-term follow-up.

PMID: 25099003 [PubMed - in process]

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[A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy].

Posted by rob on August 7, 2014 under Uncategorized | Comments are off for this article

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[A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy].

Kansenshogaku Zasshi. 2014 May;88(3 Suppl 9-10):33-6

Authors: Suzuki K, Sekine T

Abstract

A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.

PMID: 24979952 [PubMed - indexed for MEDLINE]

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LIFR?-CT3 induces differentiation of a human acute myelogenous leukemia cell line HL-60 by suppressing miR-155 expression through the JAK/STAT Pathway.

Posted by rob on August 6, 2014 under Uncategorized | Comments are off for this article

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LIFR?-CT3 induces differentiation of a human acute myelogenous leukemia cell line HL-60 by suppressing miR-155 expression through the JAK/STAT Pathway.

Leuk Res. 2014 Jul 22;

Authors: Xu S, Xu Z, Liu B, Sun Q, Yang L, Wang J, Wang Y, Liu H

Abstract

The distal cytoplasmic motifs of the leukemia inhibitory factor receptor ?-chain (LIFR?-CT3) and its TAT fusion protein (TAT-CT3) can independently suppress cell viability and induce myeloid differentiation in human leukemia HL-60 cells in our previous studies. But its underlying mechanism remains undefined. Herein, we show that a prokaryotic expressed TAT-CT3 induced a rapid elevation of STAT3 phosphorylation (pSTAT3), and then suppress the transcription of miR-155 and induce the elevation of SOCS-1, which further inhibited STAT3 phosphorylation for a long-term period. Our result indicated a novel mechanism of TAT-CT3 to promote HL60 cells differentiation, which provides some potential therapeutic targets for future acute myelogenous leukemia therapy.

PMID: 25092123 [PubMed - as supplied by publisher]

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