Treatment Outcome of Multidrug Resistance Related mRNA Expression and c-Jun-N-Terminal Kinase Activity in Patients with Acute Myeloid Leukemia / 대한진단검사의학회지

BACKGROUND: The multidrug resistance (mdr1), multidrug resistance associated protein (mrp1), and glutathione-s-transferase (gst) pi genes have been associated with treatment failure in acute myeloid leukemia (AML). c-jun N-terminal kinase (JNK) activity is increased in response to chemotherapeutic agent. METHODS: To investigate the significance of multidrug resistance (mdr) parameters and JNK activity, bone marrow or peripheral blood cells from 52 patients with AML were analyzed. RT-PCR was performed for mdr1, mrp1, and gst pi gene expression. JNK expression and activity were measured using an immunoe- nzymatic kinase assay and a western blot method. RESULTS: High level expression of mdr1, mrp1, and gst pi mRNA was observed in 38.5%, 48.1% and 54.3% of AML cases, respectively. The remission rate was significantly low in cases with an older age (>55 yr), a high WBC count, poor chromosomal abnormalities, a high level expression of mdr1 and mrp1. The WBC count and mdr1 mRNA expression were independent predictors for the outcome to induction chemotherapy. There was a shorter duration of overall survival in the patients with an older age, a high WBC count, chromosome aberrations, high level expressions of mdr1 and mrp1 mRNA, and JNK activation. The patient's age, WBC count and chromosomal abnormalities were independent predictors for overall survivals. The majority (28/30) of AML cases did not show any levels of JNK activation except for two cases, which were associated with an extremely high WBC count, chromosomal aberration, high level expressions of mdr1, mrp1 and gst pi mRNA, and treatment resistance. CONCLUSIONS: These data indicate the influences of mdr1 and mrp1 mRNA expression on the clinical outcome of AML to induction chemotherapy. But it will be necessary to investigate further whether blast cells of AML resistant to chemotherapy retain the capacity to activate JNK, and relate to MDR parameters.

Clinical Usefulness of Measurement of Reticulated Platelets by Thiazole Orange in Idiopathic Thrombocytopenic Purpura / 대한임상병리학회지

BACKGROUND: Reticulated platelets (RP) are young platelets with a high mRNA that are newly produced from the bone marrow. Thiazole orange (TO) has been a RNA staining fluorescent dye for reticulocyte, and used for RP recently. The increased percentage of RP (RP%) reflects immaturity and hematopoietic activity of platelets, therefore it may be useful for the diagnosis of idiopathic thrombocytopenic purpura (ITP). METHODS: To assess the usefulness of RP in diagnosing ITP, we compared with RP%s of 50 ITP patients, 35 thrombocytopenic patients due to impaired production and 87 heathly normal controls. Platelets were stained with TO dye, followed by flowcytometric analysis. Platelet associated IgG (PAIgG) was also measured with the same samples. The standard gate was used as a reference with the unstained sample from a normal subject and the RP% was expressed as the percentage of TO positive cells of platelets. RESULTS: The RP% of patients with ITP was significantly higher than those of thrombocytopenia due to impaired platelet production and healthy controls (24.4+/-14.3% vs 8.6+/-5.2% and 8.0+/-5.1%, respectively). There was negative correlation between the platelet count and RP%, and positive correlation between MPV and RP%. In diagnosing for ITP, the sensistivity and specificity of RP% were 81% and 92%, respectively, and more valuable than those of PAIgG test. Using RP% and PAIgG at the same time, the diagnostic efficiency for ITP was not improved. The RP% of an ITP patient was changed to correspond with the disease progression, and that of an AML patient following chemotherapy was increased to precede the rising of the platelet count. CONCLUSION: It suggest that the measurement of reticulated platelets is a very useful test for diagnosis of ITP, furthermore it can be used to estimate the thrombopoietic activity before bone marrow examination.

Measurement of Serum sIL-2R, sCD8 and TNF-alpha Levels in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia / 대한임상병리학회지

BACKGROUND: Soluble IL-2R, soluble CD8 and TNF-alpha are elevated in sera of some patients with hematological malignancies, and a marked elevation of these cytokines could be used to assess disease activity and prognosis in this malignancy group. METHODS: The serum levels of sIL-2R, sCD8 and TNF-alpha were assessed in 28 patients with myelodysplastic syndrome (MDS) and 32 patients with acute myeloid leukemia (AML), and 39 cases of healthy control subjects to define clinical usefulness as prognostic markers by sandwich enzyme immunoassay. RESULTS: In MDS patients, serum sIL-2R levels were significantly higher as compared with controls, and a more pronounced increase of serum sIL-2R levels was found in patients with RAEB RAEB-t and CMML as compared with RA and RARS. Serum sCD8 levels were higher as compared with controls, but not related with FAB classification. In patients with leukemic conversion. sCD8 levels tended to be higher as compared with patients with non-conversion. The sIL-2R levels of AML patients were significantly higher than controls, and a significant correlation was detected between the levels of sIL-2R and WBC counts. Higher sIL-2R levels( >2000 U/ml) tended to affect both complete remission rate and survival. Serum sCD8 levels were higher than controls, but not related to FAB classification. No differences of serum TNF-alpha levels were detected as compared with healthy controls. CONCLUSIONS: From these results, this study indicates that serum sIL-2R and sCD8 are significantly increased in some patients with MDS and AML, and increased levels of serum sIL-2R and sCD8 may be useful for predicting prognosis of these patients.