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Raymond Wai-Ming Lung,
Xingyan Wang,
Joanna Hung-Man Tong,
Shuk-Ling Chau,
Kin-Mang Lau,
Shuk-Hang Cheng,
John Kong-Sang Woo,
Jean Woo,
Ping-Chung Leung, Margaret Heung-Ling Ng,
Nelson Leung-Sang Tang,
Ka-Fai To
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ABSTRACT: A common GC polymorphism within miRNA-146a precursor region (rs2910164) has been associated with the risk of various cancers despite the underlying mechanism is unclear. In the current study, we aimed to examine the role of rs2910164 in the pathogenesis and predisposition to nasopharyngeal carcinoma (NPC). The GC polymorphism in 233 NPC patients, 173 matched controls and 3613 healthy elderly subjects in our locality were first determined using melting temperature (T(m) )-shift allele-specific genotyping method. Results in our case-control study indicated that CC genotype was associated with the risk effect of NPC (adjusted odds ratio of GC + GG vs. CC, 0.49; 95% confidence interval, 0.35-0.69; P < 0.0001). Using real-time polymerase chain reaction (PCR) assay, we subsequently revealed that expressions of both miR-146a and its passenger strand (miR-146a*C or miR-146a*G) were increased in NPC samples (P < 0.001), albeit expression of miR-146a was not linked to the genotype. Furthermore, miR-146a*C in NPC was significantly increased in CC genotype (CC vs. GC, P = 0.038). Finally, we demonstrated by co-immunoprecipitation and luciferase reporter assays that all three miR-146a precursor-derived mature miRNAs interacted with Argonaute2 (Ago2) protein complex and could function as gene silencers. Taken together, our results showed that the variant C in rs2910164 was associated with the predisposition of NPC in Chinese population. This polymorphism may influence the risk of NPC by producing active mature miR-146a*C that regulate distinct set of target genes. These findings may enrich our understanding of how miRNA single nucleotide polymorphism affect NPC pathogenesis, and may have potential implications to improve NPC treatment in the future. © 2012 Wiley Periodicals, Inc.
Molecular Carcinogenesis 06/2012; · 3.16 Impact Factor
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ABSTRACT: The mammalian target of rapamycin (mTOR) and the microtubules are prominent druggable targets for hepatocellular carcinoma (HCC). PI3K/Akt/mTOR activation is associated with resistance to microtubule inhibitors. Here, we hypothesized that co-targeting of mTOR (by mTOR inhibitor temsirolimus) and the microtubule (by microtubule-destabilizing agent vinblastine) would be more efficacious than single targeting in HCC models. In vitro studies showed that effective inhibition of mTOR signaling with temsirolimus alone was able to suppress HCC cell growth in a dose-dependent manner. Among five cell lines tested, Huh7 was the most temsirolimus-sensitive (IC(50)=1.27±0.06μM), while Hep3B was the most temsirolimus-resistant (IC(50)=52.95±17.14μM). We found that co-targeting of mTOR (by temsirolimus) and the microtubule (by vinblastine, at low nM) resulted in marked growth inhibition in Huh7 cells and synergistic growth inhibition in Hep3B cells (achieving maximal growth inhibition of 80-90%), demonstrating potent antitumor activity of this novel combination. In vivo studies showed that temsirolimus treatment alone for 1 week was able to inhibit the growth of Huh7 xenografts. Strikingly, the temsirolimus/vinblastine combination induced a significant and sustained antitumor activity (up to 27 days post-treatment), with effective reduction of tumor vessel density in both Huh7 and Hep3B xenograft models. Mechanistic investigation revealed that this marked antitumor effect was accompanied by specific and concerted down-regulation of several key anti-apoptotic/survival proteins (survivin, Bcl-2, and Mcl-1), which was not observed in single agent treatments. Our findings demonstrated that the potent anti-cancer activity of this co-targeting strategy was indeed mediated in parts by inhibition of these key survival/anti-apoptotic proteins.
Biochemical pharmacology 01/2012; 83(9):1146-58. · 4.25 Impact Factor
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Samantha Wei-Man Lun,
Siu Tim Cheung,
Phyllis Fung Yi Cheung,
Ka-Fai To,
John Kong-Sang Woo,
Kwong-Wai Choy,
Chit Chow,
Chartia Ching-Mei Cheung,
Grace Tin-Yun Chung,
Alice Suk-Hang Cheng,
Chun-Wai Ko,
Sai-Wah Tsao,
Pierre Busson, Margaret Heung-Ling Ng,
Kwok-Wai Lo
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ABSTRACT: Nasopharyngeal carcinoma (NPC) is a unique EBV-associated epithelial malignancy, showing highly invasive and metastatic phenotype. Despite increasing evidence demonstrating the critical role of cancer stem-like cells (CSCs) in the maintenance and progression of tumors in a variety of malignancies, the existence and properties of CSC in EBV-associated NPC are largely unknown. Our study aims to elucidate the presence and role of CSCs in the pathogenesis of this malignant disease. Sphere-forming cells were isolated from an EBV-positive NPC cell line C666-1 and its tumor-initiating properties were confirmed by in vitro and in vivo assays. In these spheroids, up-regulation of multiple stem cell markers were found. By flow cytometry, we demonstrated that both CD44 and SOX2 were overexpressed in a majority of sphere-forming C666-1 cells. The CD44+SOX2+ cells was detected in a minor population in EBV-positive xenografts and primary tumors and considered as potential CSC in NPC. Notably, the isolated CD44+ NPC cells were resistant to chemotherapeutic agents and with higher spheroid formation efficiency, showing CSC properties. On the other hand, microarray analysis has revealed a number of differentially expressed genes involved in transcription regulation (e.g. FOXN4, GLI1), immune response (CCR7, IL8) and transmembrane transport (e.g. ABCC3, ABCC11) in the spheroids. Among these genes, increased expression of CCR7 in CD44+ CSCs was confirmed in NPC xenografts and primary tumors. Importantly, blocking of CCR7 abolished the sphere-forming ability of C666-1 in vitro. Expression of CCR7 was associated with recurrent disease and distant metastasis. The current study defined the specific properties of a CSC subpopulation in EBV-associated NPC. Our findings provided new insights into developing effective therapies targeting on CSCs, thereby potentiating treatment efficacy for NPC patients.
PLoS ONE 01/2012; 7(12):e52426. · 4.09 Impact Factor
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ABSTRACT: Nasopharyngeal cancer (NPC) is a highly prevalent and invasive head and neck cancer in Asia. Disease recurrence and distant metastasis account for major NPC deaths. Therefore, more effective therapy is needed. Lapatinib, a dual tyrosine kinase inhibitor (TKI) against both EGFR and HER-2, has been known to exert potent antitumor activity against several cancer models. Given that both EGFR and HER-2 are co-expressed in NPC, we hypothesized that dual targeting of EGFR and HER-2 by this small molecule EGFR/HER-2 TKI would elicit anti-tumor activity in NPC. Using in vitro models of NPC, we demonstrated that lapatinib was able to efficiently inhibit the phosphorylation of both EGFR and HER-2. This was accompanied by significant growth inhibition of NPC cells (with maximal growth inhibition >90%). For the most lapatinib-sensitive cell line (HK1-LMP1, with IC(50) ∼ 600 nM), which harbored the highest levels of both EGFR and HER-2, inhibition of cell growth was associated G(0)/G(1) cell cycle arrest, marked PARP cleavage, caspase-3 cleavage, as well as significant downregulation of several important survival proteins (e.g. survivin, Mcl-1 and cyclin D1). NPC cells are intrinsically invasive. We found that lapatinib was able to inhibit cellular invasion of both HK1-LMP1 and HONE-1 cells. Furthermore, our data demonstrated for the first time that lapatinib harbored potent anoikis-sensitization activity (i.e. sensitizing cancer cells to detachment-induced apoptosis) in human cancer cells overexpressing both EGFR and HER-2 (HK1-LMP1 and HK1). Taken together, our findings suggest that lapatinib is a promising anti-cancer agent for NPC with anti-invasion and anoikis-sensitization activities.
Investigational New Drugs 12/2011; 29(6):1241-52. · 3.36 Impact Factor
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ABSTRACT: With the use of intensive chemotherapy and hematopoietic stem cell transplantation (HSCT), the prognosis of childhood acute myeloid leukemia (AML) improved over the last 2 decades. Survival data of Chinese pediatric patients were seldom reported. The authors adopted modified UK Medical Research Council (MRC) AML protocols for treatment of childhood AML since 1994. From 1994 to 2008, the outcomes of Chinese AML patients were studied. Sixty-eight patients were studied. The median age at diagnosis was 9.9 years. Twenty-five patients (36.8%) had favorable cytogenetic karyotypes, including t(15;17), t(8;21) and inv(16). Complete remission (CR) rate was 91.2%. The relapse rate was 29.4%. For non-M3 patients, the 5-year overall survival (pOS) was 64% ± 7% and event-free survival (pEFS) was 53% ± 7%. For those non-good-risk patients who achieved CR, there were no significant differences in outcomes between patients who received HSCT in CR1 and those received chemotherapy alone (5-year pOS 80% ± 13% and 69% ± 9%, P = .52), 5-year pEFS 69% ± 15% and 55% ± 10%, P = .40). The pOS of the 20 relapsed patients was 29% ± 11%. Sixteen patients with t(8;21) and inv(16) had similar outcome with those without favorable cytogenetics (pOS 66% ± 12% versus 65% ± 7%, P = .39; pEFS 60% ± 11% versus 54% ± 8%, P = .45). Patients who achieved CR after 2 or more courses of chemotherapy and presenting white blood cell count (WBC) ≥ 100 × 10(9)/L had poorer outcome (pOS 40% versus 80%P < .01; 43% versus 70%, P = .02, respectively). Intensified chemotherapy improved outcome of Chinese AML children. CR after first course of chemotherapy and WBC at diagnosis were important prognostic factors.
Pediatric Hematology and Oncology 02/2011; 28(4):269-78. · 0.89 Impact Factor
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Brigette B Y Ma,
Vivian W Y Lui,
Fan Fong Poon,
S C Cesar Wong,
Ka-Fai To,
Elaine Wong,
Honglin Chen,
Kwok-Wai Lo,
Qian Tao, Margaret Heung Ling Ng,
Suk Hang Cheng,
Anthony T C Chan
Investigational New Drugs 02/2010; · 3.36 Impact Factor
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Vivian Wai Yan Lui,
Cecilia Pik Yuk Lau,
Crystal Sao Fong Cheung,
Kakiu Ho, Margaret Heung Ling Ng,
Suk Hang Cheng,
Bo Hong,
Sai-Wah Tsao,
Chi Man Tsang,
Kenny Ieng Kit Lei,
Yasundo Yamasaki,
Akira Mita,
Anthony T C Chan
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ABSTRACT: 1-(3-C-ethynyl-beta-d-ribo-pentofuranosyl)cytosine (ECyd) is a ribose-modified nucleoside analog of cytidine with potent anticancer activity in several cancers. The main antitumor mechanism of this promising RNA-directed nucleoside anti-metabolite is efficient blockade of RNA synthesis in cancer cells. Here, we examined the therapeutic potential of this RNA-directed anti-metabolite in in vitro models of nasopharyngeal cancer (NPC). In a panel of 6 NPC cell lines, ECyd effectively inhibited cellular proliferation at nM concentrations (IC(50): approximately 13-44nM). Moreover, cisplatin-resistant NPC cells were highly sensitive to ECyd (at nM concentration). The ECyd-mediated growth inhibition was associated with G(2)/M cell cycle arrest, PARP cleavage (a hallmark of apoptosis) and Bcl-2 downregulation, indicating induction of apoptosis by ECyd in NPC cells. Unexpectedly, ECyd-induced significant downregulation of TIGAR, a newly described dual regulator of apoptosis and glycolysis. More importantly, this novel action of ECyd on TIGAR was accompanied by marked depletion of NADPH, the major reducing power critically required for cell proliferation and survival. We hypothesized that ECyd-induced TIGAR downregulation was crucially involved in the antitumor activity of ECyd. Indeed, overexpression of TIGAR was able to rescue NPC cells from ECyd-induced growth inhibition, demonstrating a novel mechanistic action of ECyd on TIGAR. We demonstrated for the first time that an RNA-directed nucleoside analog, ECyd, exerts its antitumor activity via downregulation of a novel regulator of apoptosis, TIGAR. Moreover, ECyd may represent a novel therapy for NPC.
Biochemical pharmacology 02/2010; 79(12):1772-80. · 4.25 Impact Factor
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Brigette B Y Ma,
Vivian W Y Lui,
Fan Fong Poon,
S C Cesar Wong,
Ka Fai To,
Elaine Wong,
Honglin Chen,
Kwok Wai Lo,
Qian Tao,
Anthony T C Chan, Margaret Heung Ling Ng,
Suk Hang Cheng
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ABSTRACT: This study evaluated the preclinical activity and molecular predictors of response to gefitinib (Iressa(R), Astra Zeneca Inc, UK) in nasopharyngeal carcinoma (NPC). The activity of gefitinib was evaluated in four human NPC cell lines--HK1, HONE-1, CNE2, C666-1. A representative gefitinib-sensitive (HK1, IC(50) = 250 nM) and gefitinib-resistant cell line (HONE-1, IC(50) > 15 microM) were selected and compared for expression of epidermal growth factor receptor (EGFR) and related ligands, and activation of downstream proteins. Gefitinib induced G1 cycle arrest, apoptosis and inhibited cell invasion more significantly in HK1 than HONE-1 cells. HK1 expressed higher levels of p-EGFR, lower p-AKT and phospho-signal transducer and activator of transcription 3 (p-STAT3) than other cell lines. EGFR gene was found to be amplified in HK1. Gefitinib at IC(50) concentrations significantly suppressed EGF-induced activation of p-EGFR, phospho-mitogen-activated protein kinase (p-MAPK) and p-STAT3, but p-AKT showed persistent activation in HK1 and HONE-1 cells. There was no difference in EGFR-ligand expression between the 4 NPC cell lines. In NPC samples derived from non-responders to gefitinib, 50% and 60% showed cytoplasmic and nuclear pi-EGFR expression, respectively, and 33% showed p-AKT expression. EGFR or KRAS mutations were not detected. This study suggests that most NPC cell lines are intrinsically resistant to gefitinib (except HK1 cells), and further studies are needed to confirm whether EGFR gene amplification and persistent AKT activation may influence response to gefitinib in NPC.
Investigational New Drugs 09/2009; 28(3):326-33. · 3.36 Impact Factor
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ABSTRACT: Despite the demonstrated constitutive activation of NF-kappaB in nasopharyngeal carcinoma (NPC), the therapeutic potential of targeting this pathway has not been investigated. Here, we employed a small molecule inhibitor of NF-kappaB, DHMEQ (which mainly blocks nuclear translocation of activated NF-kappaB) and demonstrated significant inhibition of NPC cell proliferation, migration, invasion, as well as anchorage-independent growth. These antitumor effects were associated with induction of G(2)/M cell cycle arrest and apoptosis, and downregulation of NF-kappaB target genes (EGFR, cyclin D1 and survivin). This first demonstration of therapeutic benefits of NF-kappaB targeting in NPC implicates the importance of targeting this pathway in NPC.
Cancer letters 07/2009; 287(1):23-32. · 4.86 Impact Factor
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ABSTRACT: We describe a case of coexisting BCR-ABL negative myeloproliferative disorder and precursor T-cell lymphoblastic lymphoma associated with t(8;13) involving FGFR1 at 8p11 in a 14-year-old boy who presented with generalized lymphadenopathy and an abdominal mass. JAK2 mutation and FIP1L1-PDGFRalpha were not detected. RT-PCR revealed the ZNF198-FGFR1 fusion transcript in both the bone marrow (BM) and lymph node (LN) of the patient at diagnosis. Of interest, reciprocal FGFR1-ZNF198 fusion transcript was demonstrated in the BM but not LN. Also differential clonal TcRgamma gene rearrangements in the BM and LN samples were observed. These findings provide novel insights into the genetic pathogenesis.
Leukemia Research 03/2007; 31(2):235-8. · 2.92 Impact Factor
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ABSTRACT: We describe the establishment and characterization of a new myeloma-derived cell line (MM17), originating from the sacral plasmacytoma of a 54-year-old Chinese woman diagnosed with multiple myeloma (MM). MM17 was confirmed morphologically and immunophenotypically to be clonal plasma cells positive for CD38 and CD138 and negative for EBV marker. Authenticity was confirmed using comparative genomic hybridization and DNA fingerprinting studies on bone marrow aspirate, sacral tumor tissue and MM17. Combined G-banding and multicolor fluorescence in situ hybridization analyses demonstrated a primarily hypodiploid karyotype with two sidelines sharing common stemline aberrations: +6, -7, -10, -13, -14, -17, -X, der(1;17)(q10;q10), t(2;7)(q23;q11.2), t(8;14)(q24;q32) and ins(16;1)(q13;?q22q41); and a number of hypertriploid cells. The involvement of p53 alteration and cyclin E overexpression, both with relevance to the induction of chromosomal instability, was investigated in MM17 and together with two other MM derived cell lines (U266 and IM-9) for cyclin E expression. Homozygous deletion of p53 gene hitherto not reported in MM, was detected. Both MM17 and U266 with complex cytogenetic aberrations demonstrated overexpression of cyclin E1 and E2, whereas IM-9 with a normal karyotype showed cyclin E2 but not E1 overexpression. These data suggested that E1 but not E2 overexpression was associated with chromosomal abnormalities observed in MM17 and U266, which provides the first supporting evidence for the link of cyclin E and chromosomal instability in MM. This is the first characterized Chinese MM-derived cell line with homozygous p53 deletion which may serve as a valuable in vitro system for studying MM pathogenesis particularly for Chinese.
International Journal of Oncology 06/2004; 24(5):1141-8. · 2.40 Impact Factor
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ABSTRACT: We report a case of childhood de novo acute myelocytic leukemia (AML) with hyperleukocytosis with monoblastic features and deranged hemostasic function. G-band karyotyping demonstrated a previously unreported t(11;13)(q23;q14) in metaphase preparations from a fluorodeoxyuridine synchronized 1-day culture of leukophoresed cells. Multicolor fluorescence in situ hybridization revealed no cryptic rearrangements except for the translocation. Reverse transcriptase polymerase chain reaction showed no concomitant positivity of AML1/ETO, BCR/ABL, PML/RARA, and CBFbeta/MYH11 resulting from t(8;21)(q22;q22), t(9;22)(q34;q11), t(15;17)(q22;q11), and inv(16) (p13q22), respectively. This report of childhood de novo AML harboring t(11;13)(q23;q14) as the sole cytogenetic abnormality provides more data on the leukemogenesis of de novo AML with a 11q23 rearrangement.
Cancer Genetics and Cytogenetics 05/2004; 150(1):78-80. · 1.39 Impact Factor
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ABSTRACT: The identification of neuroblastoma metastases to bone marrow (BM) is requisite in staging disease for risk-adopted therapy. However, micrometastases were not elucidated fully.
Flow cytometry (FCM) with CD45/CD56/CD81 and reverse transcriptase-polymerase chain reactions (RT-PCR) for tyrosine hydroxylase (TH) transcripts were used to evaluate neuroblastoma in bilateral BM aspirates at diagnosis, BM autografts, peripheral blood stem cell (PBSC) collections, and CD34(+) cell products of 27 children.
TH transcripts were amplified in histology-negative (H(-)) BM specimens from seven patients (four patients with Stage 3 disease, two with Stage 4 disease, and one with Stage 4S disease), revealing a prevalence of submicroscopic metastasis. The median number of CD45(-)CD81(+)CD56(+) cells in four H(-) TH(-) BM samples from two patients with Stage 1 and Stage 2 disease, respectively, was comparable to that encountered in 10 normal BM controls (0.003% [range, 0.002-0.004%] vs. 0.004% [0-0.008%], P = 0.724). In six H(-) TH(+) BM specimens from three patients whom were otherwise diagnosed with neuroblastoma Stage 3, 0.031% (0.009-0.06%) CD45(-)CD81(+)CD56(+) cells were detected. Besides, 1.474% (0.088-3.009%) CD45(-)CD81(+)CD56(+) cells were identified in four H(-) TH(+) BM specimens from two patients at Stage 4. TH transcripts were evident in four of five BM autografts and in 22 of 45 (48.9%) PBSC specimens. FCM demonstrated 0.018% and 0.049% CD45(-)CD81(+)CD56(+) cells in two TH(+) BM autografts, respectively. The number of CD45(-)CD81(+)CD56(+) cells was higher in 19 TH(+) PBSC specimens than in 20 TH(-) PBSC specimens (0.026% [0.006-1.128%] vs. 0% [0-0.009%], P < 0.0001). CD34(+) cell selection achieved 2.9 (2.1-3.5) log depletion of CD45(-)CD81(+)CD56(+) cells in four manipulated products, rendering six of seven PBSC autografts TH-free.
FCM in combination with RT-PCR evaluated neuroblastoma micrometastasis and assessed the purity of hematopoietic autografts for transplant. However, the clinical relevance remains to be elucidated.
Cancer 06/2003; 97(11):2887-97. · 4.77 Impact Factor
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ABSTRACT: Thrombospondin-1 (TSP-1) is an inhibitor of angiogenesis, inducing apoptosis of the endothelial cells via CD36 signaling mechanism. We investigated CD36 expression and the effect of TSP-1 on megakaryocytopoiesis, with and without pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), and with and without blocking TSP-1 binding with receptor CD36 on megakaryocytic cells. Our data showed that TSP-1 induced a dose-dependent growth inhibition in both murine and human colony forming unit-megakaryocyte (CFU-MK) assays and significantly counteracted the mitogenic effect from PEG-rHuMGDF. Moreover, the growth suppression induced by TSP-1 was correlated with CD36 expression in megakaryocytic cell lines, where growth inhibition was demonstrated in CD36 positive (Meg-01, Dami and CHRF-288-11) but not in CD36 negative (M-07e) cell lines. More importantly, the inhibitory effect of TSP-1 on both human CFU-MK and Meg-01 cells was partially but significantly reversed by the addition of FA6-152 (anti-CD36), a blocking antibody which blocks the access of TSP-1 to CD36 receptor, suggesting that the TSP-1-induced inhibition of megakaryocytopoiesis is probably mediated in part by the binding of TSP-1 to CD36 expressed on the megakaryocytic progenitors. Thus, our findings represent the first demonstration that TSP-1 inhibits in vitro megakaryocytopoiesis via interaction with CD36.
Thrombosis Research 02/2003; 109(1):47-54. · 2.44 Impact Factor
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ABSTRACT: The TEL/AML1 rearrangement has been implicated as an independent good prognostic factor in pediatric acute lymphoblastic leukemia (ALL). We examined TEL/AML1 using nested reverse-transcription polymerase chain reaction (RT-PCR) and correlated TEL/AML1 with cytogenetics and immunophenotypes in 75 consecutively analyzed Chinese children with ALL in Hong Kong. TEL/AML1 was detected in 17.9% (12/67) B-lineage ALL at diagnosis but not in 8 T-ALL children or in 34 adults with ALL. E2A/PBX1, MLL/AF4, and BCR/ABL were not found in TEL/AML1+ patients. Coexpression of cross-lineage antigens was associated with TEL/AML1 gene fusion (p = 0.032), with CD13 in 80% (4/5) TEL/AML1+ cohort. Chromosomal abnormalities were demonstrated in 50% of the TEL/AML1+ ALL; however, a cryptic t(12;21) was not detected in these cases. Hyperdiploidy of 47–48 chromosomes was encountered in 25%. Deletion of 12p resulting in the loss of the normal allele of TEL and nonspecific del(6q) were noted in 8% (1/12) and 25% (3/12) of the TEL/AML1+ children, respectively. Rapid clearance of TEL/AML1 was noted in 50% of the patients on completion of the induction therapy; however, 16.7% (2/12) TEL/AML1+ ALL relapsed at a mean of 48.6 months from diagnosis (25 months off-therapy). The incidence of relapses of TEL/AML1+ ALL was comparable to that at diagnosis in B-lineage ALL (14.3% [2/14] vs. 17.9% [12/67], p > 0.05). The relapse rate in TEL/AML1+ ALL was similar to that of TEL/AML1− ALL (16.7% [2/12] vs. 20.6% [13/63], p > 0.05). The duration of first complete remission in TEL/AML1+ ALL was significantly longer as compared to TEL/AML1− ALL (mean [range] in month: 48.6 [47.2 − 50] vs 14.6 [2.9 − 42.3], p < 0.0001). Irrespective of TEL/AML1 rearrangement, the probabilities of the five-year overall survival and the event-free survival of patients were comparable (overall survival: 100% vs. 72.3%, p = 0.166 and event-free survival: 60% vs. 56.2%, p = 0.343). Our data would not suggest a less aggressive treatment regimen for TEL/AML1+ ALL. Am. J. Hematol. 68:91–98, 2001. © 2001 Wiley-Liss, Inc.
American Journal of Hematology 09/2001; 68(2):91 - 98. · 4.67 Impact Factor
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ABSTRACT: We report here a family of patients with coexistent hereditary spherocytosis and α-thalassaemia. The different clinical presentations of the family members were affected by the severity of the α-thalassaemia. The haemolytic effect of hereditary spherocytosis was modulated by the increased osmotic resistance of thalassaemia in the patients with both disorders. Coexistence of haemoglobin H disease and hereditary spherocytosis resulted in an asymptomatic state. In contrast, coexistence of α-thalassaemia trait and hereditary spherocytosis was still haemolytic. The different shapes of the osmotic curves in the family members correlated with the severity of their symptoms.
Acta Haematologica. 08/1970; 91(4):201-205.
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ABSTRACT: Cytogenetic investigation of multiple myeloma (MM) has been difficult by conventional methods and most of the data have been derived from western population where incidence of MM is much higher as compared to that of Asians. The current study represents the first report of chromosomal aberrations of multiple myeloma in Chinese. We investigated 25 consecutive Chinese patients with MM for chromosomal aberrations at diagnosis using G-banding and multicolor spectral karyotyping (SKY). Of the 21 patients successfully analyzed by G-banding, 11 patients revealed cytogenetic abnormalities showing complex numerical and structural aberrations, which were further characterized with SKY. An abnormal karyotype significantly associated with blastic MM was observed. Consistent with the western literature, structural rearrangements involving chromosomes 1, 6, 8, 19, numerical abnormalities of gains in chromosomes 9, 3, and 5, and losses in chromosomes 13 and 14 were observed. However, there were notably higher incidences of -22/22q- (4/11) and structural aberrations of chromosome X but a lower incidence of -X. The biological implications of these findings, if confirmed, deserve further evaluation.
Oncology Reports 10(3):587-91. · 1.84 Impact Factor
