Study of Water Relative Permeability in Fractures Using Well Tests and Radon: Gas Bubbles Effect.

Few published data are available for two-phase flow in fractures from field studies. All measurements of relative permeability reported in the literature were done in laboratory-scale. The in situ water saturations are normally not known for multiphase flow in natural fractures; therefore, the direct measurements of relative permeability are difficult in field-scale. With the help of a case study before and after the 2008 Mw 5.4 Antung earthquake, groundwater radon was used as a tracer to determine the gas and water saturations in a small naturally fractured aquifer. Well tests were also conducted to estimate aquifer transmissivity before and after the 2008 Antung earthquake. Anomalous declines in both groundwater radon concentration and transmissivity were observed precursory to the 2008 Antung earthquake. Both declines are two precursory phenomena having a common effect of gas bubbles. Using the data from well tests and radon tracer, one data point of water relative permeability can be obtained for in situ fractures. This data point reveals strong phase interference between water and gas bubbles for multiphase flow in natural fractures. Both the data of well tests and radon tracer are essential to gain an improved understanding of mass transfer behavior of groundwater-dissolved gases between water and gas phases.

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.

Are structural characteristics of programs and hospitals associated with 100-day readmission of hematopoietic SCTs in Taiwan?

Hematopoietic SCT (HSCT) is one treatment modality for hematological malignancies. It is increasingly common but remains centralized in certain hospitals wherein procedures and protocols can vary. This study examined 100-day readmission for patients with hematological malignancies undergoing HSCT in Taiwan from the years 2001 to 2006. Of particular interest was an examination of how HSCT program characteristics might influence outcomes. This population-based retrospective cohort study with longitudinal follow-up used Taiwan's National Health Insurance Research Database. A generalized linear model with a logistic-dependent variable representing being admitted or not admitted was used to model 100-day readmission, adjusting for the nested design. There were 718 HSCT recipients for hematological malignancies in the 5-year study period from 10 HSCT programs. In spite of the average length of stay of 43.71 days (s.d.=25.75) days, 52% of recipients were readmitted within 100 days of discharge. Ownership status, the number of HSCT hematologists, and the ratio of HSCT procedures to HSCT hematologists independently predicted 100-day readmission after adjusting for clustered data and controlling for recipient characteristics.

Role of serum sodium in assessing hospital mortality in cancer patients with spontaneous tumour lysis syndrome inducing acute uric acid nephropathy.

Spontaneous tumour lysis syndrome (STLS) inducing acute uric acid nephropathy, a rare and neglected disease, presents more insidiously than conventional post-treatment tumour lysis syndrome. Although STLS is a serious and potentially fatal complication in patients with neoplastic disorders, few investigations have addressed the relevance of clinical and laboratory features in assessing prognosis. A retrospective study was conducted, reviewing the records of all patients who developed acute renal failure (ARF) at Chang Gung memorial hospital between 1 July 1999 and 30 June 2003. STLS-induced acute uric acid nephropathy was identified in 12 of 1072 ARF patients (1.1%) during the study period. All patients had advanced stage tumours with large tumour burden, and 66.7% of cases had abdominal organ involvement. All 12 hyperuricemic patients became oliguric despite conservative therapy, and remained hyperuricemic (21.6 +/- 5.2 mg/dl) before dialysis therapy. Diuresis developed in eight patients (66.7%), with associated resolution of hyperuricemia, azotemia and metabolic derangements following dialysis initiation. Overall hospital mortality was 58.3%. Death in most patients was related to hyponatremia and hypoalbuminemia on admission. The serum sodium was found to have the best Youden index (0.86) and highest overall prediction accuracy (93%). Moreover, serum sodium and serum albumin for individual patients were significantly and positively correlated (r = 0.617, p = 0.032). This investigation confirms a grave prognosis for cancer patients with STLS inducing acute uric acid nephropathy. Hyponatremia and hypoalbuminemia on the first day of admission indicate poor prognosis in such patients.

RUNX1 mutations are frequent in chronic myelomonocytic leukemia and mutations at the C-terminal region might predict acute myeloid leukemia transformation.

Runt-related transcription factor 1 (RUNX1) is essential for normal hematopoiesis. RUNX1 mutations have rarely been reported in chronic myelomonocytic leukemia (CMML). We examined RUNX1 mutations in 81 patients with CMML at initial diagnosis. Mutational analysis was performed on bone marrow samples by direct sequencing of all reverse transcription PCR products amplified with three primer pairs that cover the entire coding sequences of RUNX1b. Thirty-two RUNX1 mutations were detected in 30 patients (37%); 23 mutants were located in the N-terminal part and 9 in the C-terminal region. The mutations consisted of 9 missense, 1 silent, 7 nonsense and 15 frameshift mutations. Two patients had biallelic heterozygous mutations. There was no difference in overall survival between patients with and without RUNX1 mutations, but a trend of higher risk of acute myeloid leukemia (AML) progression was observed in mutation-positive patients (16/30 vs 17/51, P=0.102), especially in patients with C-terminal mutations (P=0.023). The median time to AML progression was 6.8 months in patients with C-terminal mutations compared with 28.3 months in those without mutations (P=0.022). This study showed for the first time a high frequency of RUNX1 mutations in CMML. C-terminal mutations might be associated with a more frequent and rapid AML transformation.

Complications impaired endothelial progenitor cell function in Type 2 diabetic patients with or without critical leg ischaemia: implication for impaired neovascularization in diabetes.

AIMS: This study tested the hypothesis that migratory function of endothelial progenitor cells (EPCs) is impaired in Type 2 diabetic patients with or without critical leg ischaemia. METHODS: Seventy-four patients were classified into four groups: Type 2 diabetic (n = 21) and non-diabetic patients (n = 10) with critical leg ischaemia and Type 2 diabetic patients without lower extremity vascular disease (n = 30) and healthy subjects (n = 13). The number and functional activity of circulating and cultured EPCs were determined. RESULTS: The migratory function of cultured EPCs was significantly impaired in diabetic patients without (median, 48, interquartile range, 46, 49 count/view/well) and with (median, 51, interquartile range, 46, 60 count/view/well) critical leg ischaemia and non-diabetic patients with critical leg ischaemia (median, 49, interquartile range, 47, 55 count/view/well) compared with healthy subjects (median, 63, interquartile range, 57, 65 count/view/well) (P < 0.0001). The number of circulating EPCs was lower in Type 2 diabetic patients without lower extremity vascular disease (median, 3500, interquartile range, 1600, 6600/10(6) cytometric events) than Type 2 diabetic patients with critical leg ischaemia (median, 5300, interquartile range, 2400, 11,100/10(6) cytometric events), non-diabetic patients with critical leg ischaemia (median, 5550, interquartile range, 2000, 32,100/10(6) cytometric events) and healthy subjects (median, 5400, interquartile range, 2700, 8700/10(6) cytometric events) (P = 0.413). CONCLUSIONS: The migratory function of EPCs is impaired in patients with Type 2 diabetes, even in those without critical leg ischaemia. These findings present an important new insight into the pathogenesis of impaired neovascularization and critical limb ischaemia in diabetic patients and provide avenues of future clinical study.

Aristolochic acid nephropathy due to herbal drug intake manifested differently as Fanconi's syndrome and end-stage renal failure--a 7-year follow-up.

Aristolochic acid (AA) may reduce glomerular or proximal tubular function, or both. We report a married couple taking AA-containing herbal drugs. The man developed Fanconi's syndrome (FS) whereas his wife reached end-stage renal failure (ESRF). He was a 36-year-old alcoholic cirrhotic patient who had taken the Chinese herbal drugs for 6 years, presenting with muscle weakness and laboratory findings of FS; the renal pathological findings were compatible with the diagnosis of aristolochic acid nephropathy (AAN). His 38-year-old wife, who took a lower cumulative amount of the same herbal drug for a shorter duration, developed advanced renal failure and severe anemia with pathological findings of extensive tubular atrophy, interstitial fibrosis but spared glomeruli. AA-I was detected in one of the herbal drugs. The wife has been on hemodialysis for 7 years, but the husband is still at the stage of slowly progressive chronic renal failure and persistent FS. None of their 5 children ever took the herbal drug, and none had renal problems during follow-up. It is important to trace the history of herbal drug intake in all the family members because of the possibility of sharing of drugs within a family. In addition to the effect of cumulative doses of AAs and the potentially higher susceptibility of females to AAN, the roles of liver cirrhosis and related vasodilators in the protection of the renal interstitium from fibrosis are questions that warrant further study.

Isoflurane preconditioning-induced cardio-protection in patients undergoing coronary artery bypass grafting.

BACKGROUND AND OBJECTIVES: Ischaemic preconditioning is commonly regarded as one of the most powerful protective mechanisms against a subsequent lethal ischaemic injury during coronary artery bypass graft surgery but is not practiced routinely. Experimentally, isoflurane, a commonly used volatile anaesthetic agent, provides myocardial protection through a signal transduction cascade that is remarkably similar to the pathways identified in ischaemic preconditioning. The aim of our study was to investigate whether pre-ischaemic administration of isoflurane exerted protection against prolonged ischaemia with functional recovery and reduced necrosis among patients undergoing coronary artery bypass graft surgery. METHODS: Forty patients scheduled for elective coronary artery bypass graft operations were prospectively randomized into the control or isoflurane groups. In the isoflurane group, isoflurane 2.5 minimum alveolar concentration was administered for 15 min followed by a 5-min washout period before aortic cross-clamping. The control group received a time-matched period of isoflurane-free cardiopulmonary bypass. The conduction of anaesthesia and surgery were standardized in all patients. Haemodynamic data, troponin I release and inotropic support were measured and recorded perioperatively. RESULTS: There were no adverse effects related to isoflurane administration. In the isoflurane group, the mean cardiac index after cardiopulmonary bypass was significantly higher than the pre-bypass value (P < 0.05), whereas no difference was found in the control group. At 15 min after cardiopulmonary bypass and 6 h after surgery, the changes in cardiac index and stroke volume index were significantly higher in the isoflurane group than in the control group (P < 0.05). There was a consistently lower release of troponin I in the isoflurane group compared to the control group. Compared to the controls, the mean troponin I level was significantly reduced in the isoflurane group at 24 h after surgery (P = 0.042). CONCLUSIONS: The present results support the preconditioning effect of isoflurane in patients undergoing coronary artery bypass graft surgery as clinically feasible and providing optimal cardiac protection.

AML patients with CEBPalpha mutations mostly retain identical mutant patterns but frequently change in allelic distribution at relapse: a comparative analysis on paired diagnosis and relapse samples.

The roles of CEBPalpha mutations and its cooperating mutations in the relapse of acute myeloid leukemia (AML) are not clear. CEBPalpha mutations were analyzed on 149 patients with de novo AML at both diagnosis and relapse. Twenty-two patients (14.8%) had the mutations at diagnosis, two patients had N-terminal nonsense mutations alone, one had homozygous inframe duplication at the bZIP domain, and 19 patients had both N-terminal and bZIP mutations. Twenty patients relapsed with identical mutant patterns, two lost CEBPalpha mutations and none acquired the mutations at relapse. Cloning analysis showed that the N-terminal and C-terminal mutations occurred on separate cloned alleles and also on the same alleles in most of the diagnosis and relapse samples. Losing one of the two or more mutations on the same allele or acquiring the other mutation on the allele original carrying single mutation were observed not infrequently in the paired samples analyzed. Seven patients with CEBPalpha mutations had cooperating mutations with FLT3/ITD, FLT3/TKD or N-ras but not K-ras mutations. Our study showed that 91% of de novo AML harboring CEBPalpha mutations at diagnosis retained the identical mutant patterns but frequently changed in the allelic distribution at relapse.

Characterization of fusion partner genes in 114 patients with de novo acute myeloid leukemia and MLL rearrangement.

The fusion transcripts of MLL rearrangement [MLL(+)] in acute myeloid leukemia (AML) and their clinicohematologic correlation have not be well characterized in the previous studies. We used Southern blot analysis to screen MLL(+) in de novo AML. Reverse transcriptase-polymerase chain reaction was used to detect the common MLL fusion transcripts. cDNA panhandle PCR was used to identify infrequent or unknown MLL partner genes. MLL(+) was identified in 114 (98 adults) of 988 AML patients. MLL fusion transcripts comprised of 63 partial tandem duplication of MLL (MLL-PTD), 14 MLL-AF9, 9 MLL-AF10, 9 MLL-ELL, 8 MLL-AF6, 4 MLL-ENL and one each of MLL-AF1, MLL-AF4, MLL-MSF, MLL-LCX, MLL-LARG, MLL-SEPT6 and MLL-CBL. The frequency of MLL-PTD was 7.1% in adults and 0.9% in children (P<0.001). 11q23 abnormalities were detected in 64% of MLL/t11q23 and in none of MLL-PTD by conventional cytogenetics. There were no differences in remission rate, event-free survival and overall survival between adult MLL-PTD and MLL/t11q23 groups. Adult patients had a significantly poorer outcome than children. The present study showed that cDNA panhandle PCR can identify all rare or novel MLL partner genes. MLL-PTD was rare in childhood AML. MLL(+) adults had a poor outcome with no difference in survival between MLL-PTD and MLL/t11q23 groups.

Pseudo-Gaucher cells in mycobacterial infection: a report of two cases.

This report describes two cases of mycobacterial infection with pseudo-Gaucher cells. Both patients had no clinical evidence of inherited Gaucher disease. The first case was a patient with AIDS and Mycobacterium avium intracellulare involving the lung, spleen, and bone marrow. The bone marrow aspirates showed many histiocytes with needle-like inclusions. Acid fast staining showed that these histiocytes contained acid fast bacilli. Bone marrow biopsies revealed granulomatous lesions with aggregates of foamy histiocytes. The second case was an alcoholic patient with Mycobacteriumkanasassi infection involving the lung and lymph nodes. The lymph node aspirates showed infiltration of the same cells with acid fast bacilli in the cytoplasm.

Acute leukaemia in chronic hepatitis B patients with lamivudine therapy.

Extensive clinical data have shown that lamivudine is an effective and safe drug for patients with chronic hepatitis B virus infection. No significant serious side effect has been reported. Four hundred and forty-eight patients with chronic hepatitis B, treated with lamivudine for more than 6 months, were closely monitored. Two patients developed acute myeloid leukaemia during or after lamivudine therapy. The first case developed acute myeloid leukaemia, 1 year after stopping lamivudine therapy, when A529T mutant HBV-DNA was still detectable. The second case achieved complete virological response but suffered from acute myeloid leukaemia during the ninth month of lamivudine treatment. D553N mutant hepatitis B virus was detected in granulocytes of her peripheral blood. Based on our lamivudine therapy data, the calculated incidence of acute myeloid leukaemia in patients during or after lamivudine therapy was higher in males and females than that of the general population. Whether lamivudine-selected viral mutations have enhanced activity/production of transcriptional transactivator and thereby increased the chance of leukaemic transformation of haematopoietic progenitor cells deserves further investigation.

Acquisition of FLT3 or N-ras mutations is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia.

The role of internal tandem duplication of fms-like tyrosine kinase 3 (FLT3/ITD), mutations at tyrosine kinase domain (FLT3/TKD) and N-ras mutations in the transformation of myelodysplastic syndrome (MDS) to AML was investigated in 82 MDS patients who later progressed to AML; 70 of them had paired marrow samples at diagnosis of MDS and AML available for comparative analysis. Five of the 82 patients had FLT3/ITD at presentation. Of the 70 paired samples, seven patients acquired FLT3/ITD during AML evolution. The incidence of FLT3/ITD at diagnosis of MDS was significantly lower than that at AML transformation (3/70 vs 10/70, P<0.001). FLT3/ITD(+) patients progressed to AML more rapidly than FLT3/ITD(-) patients (2.5+/-0.5 vs 11.9+/-1.5 months, P=0.114). FLT3/ITD(+) patients had a significantly shorter survival than FLT3/ITD(-) patients (5.6+/-1.3 vs 18.0+/-1.7 months, P=0.0008). After AML transformation, FLT3/ITD was also associated with an adverse prognosis. One patient had FLT3/TKD mutation (D835Y) at both MDS and AML stages. Additional three acquired FLT3/TKD (one each with D835 H, D835F and I836S) at AML transformation. Five of the 70 matched samples had N-ras mutation at diagnosis of MDS compared to 15 at AML transformation (P<0.001), one lost and 11 gained N-ras mutations at AML progression. Coexistence of FLT3/TKD and N-ras mutations was found in two AML samples. N-ras mutations had no prognostic impact either at the MDS or AML stage. Our results show that one-third of MDS patients acquire activating mutations of FLT3 or N-ras gene during AML evolution and FLT3/ITD predicts a poor outcome in MDS.

All- trans-retinoic acid-induced erythema nodosum in patients with acute promyelocytic leukemia.

Erythema nodosum associated with all- trans-retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is very rare. We describe four patients with classic APL who developed erythema nodosum during ATRA therapy. Fever and subsequent multiple painful erythematous nodules over extremities developed on D11, D16, D17, and D19, respectively, after ATRA therapy. The skin biopsy taken from each patient was consistent with erythema nodosum. All patients received short course of steroids. Fever subsided rapidly and the skin lesions regressed completely. All patients achieved complete remission without withdrawal of ATRA. ATRA seemed to be the most possible etiology of erythema nodosum in our patients. Short-term use of steroid is very effective in ATRA-induced erythema nodosum.

The synergistic effect of thrombopoietin in erythropoiesis with erythropoietin and/or IL-3 and myelopoiesis with G-CSF or IL-3 from umbilical cord blood cells of full-term neonates.

The authors sought to determine whether recombinant human thrombopoietin (TPO) acts synergistically with other cytokines on burst-forming unit-erythroid (BFU-E)-derived and colony-forming unit-granulocyte/macrophage (CFU-GM)-derived colony formations from cord blood. Cord blood nonadherent mononuclear cells (MNC) from normal full-term neonates were cultured in a methylcellulose system. When cultured with 5 x 10(4) MNC/mL, erythropoietin (EPO) 2 U/mL, interleukin-3 (IL-3) 50 ng/mL, and/or TPO 400 ng/mL (experiment 1), the addition of TPO to EPO gave rise to more BFU-E-derived colonies (p = .002). The addition of TPO to EPO + IL-3 gave rise to more BFU-E-derived colonies (p = .006) also. TPO synergizes erythropoiesis from cord blood. When cultured with IL-3 50 ng/mL, granulocyte colony-stimulating factor (G-CSF) 25 ng/mL, and/or TPO 400 ng/mL, the addition of TPO to IL-3 gave rise to more CFU-GM-derived colonies (p = .002). The addition of TPO to G-CSF gave rise to more CFU-GM-derived colonies (p = .002) also. TPO synergizes myelopoiesis from cord blood. Thus, TPO has synergistic effects on both erythropoiesis and myelopoiesis from cord blood. In the identical conditions of culture, cord blood had significantly greater BFU-E-derived or CFU-GM-derived colony formation than bone marrow (in a previous report by the authors) did. When cultured under conditions similar to those of experiment 1, but with 1 x 10(4) cord blood MNC/mL and TPO 100 ng/mL (experiment 2), results similar to those in the experiment 1 also revealed that TPO has synergistic effects on erythropoiesis and myelopoiesis from cord blood. In every individual assay, the numbers of BFU-E-derived or CFU-GM-derived colonies in experiment 1 were significantly higher than those in experiment 2.

Clonality analysis using X-chromosome inactivation patterns by HUMARA-PCR assay in female controls and patients with idiopathic thrombocytosis in Taiwan.

OBJECTIVE: Analysis of X-chromosome inactivation patterns (XCIPs) is a useful tool in the diagnosis of clonal disorders. The human androgen receptor (HUMARA) locus is especially useful for clonality study. The present study was conducted 1) to determine the heterozygosity rate for HUMARA locus in Taiwanese women, 2) to determine the frequency of excessive skewing in different cell types, and 3) to determine the utility of XCIPs in the differential diagnosis of thrombocytosis. PATIENTS AND METHODS: XCIPs by HUMARA-PCR assay were performed on purified granulocytes and T cells from 73 female patients presenting with idiopathic persistent thrombocytosis (IT), 10 patients with reactive thrombocytosis (RT), and 46 bone marrow samples from female controls. XCIPs of buccal mucosa cells were also compared with those of T cells in 57 patients with IT. The percentage of clonal granulocytes was calculated after correcting for the degree of Lyonization in T cells. RESULTS: The heterozygosity rate for the HUMARA gene was 89.1% in Taiwanese females. The median age of informative IT patients and controls was 59 (18-92) and 58 (19-89), respectively. Excessive skewing (allele ratio <0.33) was more frequent in granulocytes than in T cells in both controls (12/43 vs 9/43, p = 0.080) and IT patients (56/64 vs 25/64, p < 0.001). XCIPs were the same for both buccal mucosa and T cells in 43 patients but were different in 14 patients. Of the 43 informative controls, 31 had a polyclonal pattern; an ambiguous pattern was found in nine; and the remaining three, aged 71, 73, and 80, respectively, had a clonal pattern. A clonal pattern was found in 42 IT patients, a polyclonal pattern in 12, and an ambiguous pattern in 10 of the 64 IT patients. The frequency of clonal, polyclonal, and ambiguous patterns in the 40 IT patients with age < or = 65 was 55.0%, 30.0%, and 15.0%, respectively. None of the IT patients aged >65 had a polyclonal disease. IT patients aged >65 had a significantly higher frequency of clonal pattern (p = 0.030) and a significantly lower frequency of polyclonal pattern (p = 0.002) than those with age <65. Of the eight heterozygous patients with RT, one aged 80 exhibited a clonal pattern, and the remaining seven had a polyclonal pattern. CONCLUSIONS: The present study on Taiwanese females showed a heterozygosity rate of 89.1% for the HUMARA gene. Our results confirmed that IT is a heterogeneous disorder in terms of clonality. Twenty-three percent of IT patients exhibited a greater than 20% difference in allele expression for buccal mucosa and T cells. Presence of a clonal XCIP in young patients with IT can serve as a positive marker for the diagnosis of clonal thrombocytosis, and elderly patients with polyclonal XCIPs are unlikely to have essential thrombocythemia.

Meningeal involvement in B-cell chronic lymphocytic leukemia: report of two cases.

Symptomatic central nervous system (CNS) involvement in chronic lymphocytic leukemia (CLL) or its variants is rare. We report two cases of CLL with leptomeningeal involvement. Patient one was an 81-year-old male who had CLL stage C (IV) at diagnosis and developed meningeal disease 29 months later. Patient 2 was a 42-year-old male with a diagnosis of CLL stage A (II) that evolved into mixed-cell CLL/prolymphocytic leukemia (PLL) 1.5 years later, with leptomeningeal infiltration of prolymphocytes developing 26 months after initial diagnosis. Meningeal leukemia was diagnosed by cerebrospinal fluid examination, with flow cytometry showing the same immunophenotypic findings of lambda-light chain restriction as the lymphocytes in bone marrow in one patient, and with morphologic characteristics exhibiting exclusively prolymphocytes in the other patient. The CNS disease of both patients responded effectively to intrathecal chemotherapy and cranial irradiation. However, both patients died of infection, a major cause of morbidity and mortality in patients with CLL. The clinicopathologic features of these two patients indicate that, despite the rarity of CNS involvement in CLL patients, any neurologic manifestation in CLL patients should arouse suspicion of meningeal leukemia and patients should be examined and managed accordingly.

The synergistic effect of thrombopoietin in erythropoiesis and myelopoiesis from human bone marrow cells.

We sought to determine whether recombinant human thrombopoietin (TPO) acts synergistically with recombinant human erythropoietin (EPO) and/or recombinant human interleukin-3 (IL-3) on erythroid burst formation and granulocyte-macrophage colony formation from human bone marrow (BM). BM cells were from 5 adults and 15 children who underwent bone marrow examination because of a clinical suspicion of malignancy; their bone marrows as well as the complete blood counts were normal and were cultured in a methylcellulose system. TPO has a synergistic effect with EPO or EPO + IL-3 on erythropoiesis of human BM, as the addition of TPO to EPO significantly gave rise to more erythroid bursts (p = 0.0001) and the addition of TPO to EPO + IL-3 might give rise to more erythroid bursts (p = 0.05). TPO also has a synergistic effect with recombinant human granulocyte colony-stimulating factor (G-CSF) on myelopoiesis of human BM, since the addition of TPO to G-CSF gave rise to significantly more granulocyte-macrophage colonies (p = 0. 0001). Besides its well-known significant role in megakaryopoiesis, TPO also has synergistic effects on erythropoiesis and myelopoiesis.