Correlations between Janus Kinase 2 V617F Allele Burdens and Clinicohematologic Parameters in Myeloproliferative Neoplasms

BACKGROUND: This study evaluated potential correlations between the allele burden of the Janus kinase 2 (JAK2) V617F mutation and clinicohematologic characteristics in patients with myeloproliferative neoplasms (MPN). METHODS: Clinical and hematologic features were reviewed for 103 MPN patients, including patients with polycythemia vera (PV, 22 patients), essential thrombocythemia (ET, 64 patients), and primary myelofibrosis (PMF, 17 patients). JAK2 V617F allele status and allele burdens were measured by allele-specific PCR and pyrosequencing, respectively. RESULTS: The JAK2 V617F mutation was detected in 95.5%, 68.8%, and 52.9% of PV, ET, and PMF patients, respectively. JAK2 V617F-positive ET patients were significantly older and exhibited higher neutrophil fractions, a higher frequency of thrombotic events, and a higher myelofibrosis rate than JAK2 V617F-negative patients (P <0.05). PV patients carried the highest mean T allele burden (66.0%+/-24.9%) compared with ET (40.5%+/-25.2%) and PMF patients (31.5%+/-37.0%) (P =0.00). No significant correlations were detected between V617F allele burden and patient age, white blood cell count, Hb, Hct, or the platelet count for PV, ET, or PMF patients. ET patients with organomegaly had a higher JAK2 V617F allele burden (53.4%+/-23.7%) than patients without organomegaly (35.6%+/-24.3%) (P =0.03). CONCLUSIONS: The JAK2 V617F mutational status and its allele burden correlate with the clinicohematologic phenotypes of ET patients, including older age, higher neutrophil count, and greater rates of organomegaly, thrombotic events, and myelofibrosis. For PV and PMF patients, larger-scale studies involving more MPN patients are needed.

A Case of Adult B Lymphoblastic Leukemia with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3) / 대한진단검사의학회지

In B lymphoblastic leukemia/lymphoma (B-ALL/LBL), t(9;22)(q34;q11.2) and t(1;19)(q23;p13.3) are recurrent cytogenetic abnormalities. The concurrent occurrence of both abnormalities is very rare, and only 3 cases have been previously reported. Here, we report a case of adult B-ALL with ider(9)(q10)t(9;22)(q34;q11.2) and der(19)t(1;19)(q23;p13.3). A literature review revealed that ider(9) (q10)t(9;22) is a rare variant of t(9;22) with a deletion of the short arm of chromosome 9. Fifteen cases of ider(9)(q10)t(9;22) have been reported. This abnormality is specific to precursor B-lymphoid neoplasms, such as B-ALL or B-lymphoid blast phase of CML, and is associated with disease progression or short survival. The cytogenetic abnormality t(1;19) is also specific to B-ALL. In most instances of t(1;19), TCF3 is fused to PBX1; however, a few cases have identical translocations but no TCF3-PBX1 fusion, as was observed in our patient. We describe the first case of ider(9)(q10)t(9;22) in combination with TCF3-PBX1 negative t(1;19). The patient underwent imatinib therapy in addition to intensive chemotherapy, but failed to achieve remission.

Two Cases of Trisomy 19 as a Sole Chromosomal Abnormality in Myeloid Disorders / 대한진단검사의학회지

Trisomy 19 is frequently encountered in cases of chronic myeloid leukemia (CML) as a secondary abnormality: however, trisomy 19 rarely occurs as a sole chromosomal abnormality and, to date, it has only been reported in 48 hematopoietic malignancies, 1 case of adenocarcinoma and 1 case of astrocytic tumor. Here, we report two additional cases of trisomy 19 as a sole karyotypic aberration in myeloid malignancies. One of these cases involved a 6-month-old male who was diagnosed with acute myeloid leukemia minimally differentiated. His karyotype was 47,XY,+19[20]. He expired 5 days after diagnosis. Another case occurred in an 80-yr-old female who had refractory anemia with excess blasts. Her karyotype was 47,XX,+19[16]/46,XX[4]. Four months later, her peripheral blood smears suggested that the disease had progressed, but she refused further evaluation. Based on a review of the existing literature and the results of this report, trisomy 19 not only as a secondary abnormality but also as a sole karyotypic aberration is strongly associated with myeloid disorder; however, it is not preferentially found in specific FAB subgroups of myelodysplasic syndrome or acute myeloid leukemia.

Acute Myeloid Leukemia with t(8;21)(q22;q22) (AML1/ETO) in a Patient with Marked Hypocellularity and Low Blasts Count / 영남의대학술지

According to the World Health Organization (WHO) classification system, cases with t(8;21)(q22;q22) should be diagnosed as acute myeloid leukemia (AML) even with a blast count of less than 20 percent in blood or bone marrow. It is an uncommon manifestation, moreover hypocellularity is rarely observed in this subtype of leukemia. Here, we report a case of t(8;21) in a patient with marked hypocellularity of less than 5 percent and a blast count of less than 20 percent. This patient responded relatively well to chemotherapy. An allogeneic bone marrow transplantation was performed with good engraftment . This case suggests that hypocellular AML with a t(8;21) has as good a prognosis as hypercellular AML with t(8;21).

Minimal Change Disease Associated with Gastric Adenocarcinoma and Multiple Liver Metastasis / 대한신장학회잡지

A 35-years-old man was hospitalized with gene-ralized edema. 6 months ago, the patient was operated by radical subtotal gastrectomy for advanced gastric adenocarcinoma. The patient presented with multiple liver metastasis and the massive proteinuria. The patients renal biopsy revealed minimal change nephrotic syndrome and treated with prednisolone and diuretics. The patient was improved clinical symptome and decreased 24 hours urine protein. In literature reviewed, gastric carcinoma was not associated with minimal change nephrotic syndrome. We experienced advanced gastric carcinoma associated with minimal change nephrotic syndrome, thus we report it.

Localization of HBsAg and Hepatitis B Virus DNA in Renal Tissues from HBsAg Positive Patients with the Membranoproliferative Glomerulonephritis / 대한신장학회잡지

Hepatitis B virus(HBV) infection has been suggested as the etiologic agent in membranoproliferative glomerulonephritis(MPGN), but the mechanism by which HBV infection leads to MPGN in human has not been established. To localize the HBV antigen and HBV-DNA in the kidney tissue, we examined paraffin sections of kidney biopsies which were positive for HBsAg by immunohistochemical study from 13 HBV carriers with MPGN (HBV-MPGN). Polymerase chain reaction(PCR) and in situ PCR(ISP) were used for the HBV DNA amplification and localization in kidney tissues. Primers used in PCR and ISP were from the S, C, and X HBV-DNA regions. Immunohistochemical study showed HBsAg deposits on the mesangium and glomerular capillaries. Arteriolar deposits were also occasionally observed. PCR for the S, C, and X regions were positive in 11 patients(85%), 11 patients(85%), and 9 patients (69%), respectively. The PCR findings were further confirmed by direct sequencing of PCR products and the amplification of HSP70 gene as a control. ISP showed the amplified HBV-DNA at the glomeruli and renal tubules. For S region, ISP was positive in 7 patients. For C and X regions, ISP was positive in 8 patients, respectively. 5 patients showed the positive signals for both the glomeruli and tubules, while 4 patients were positive at the tubules only. These 4 patients seemed to have the longer disease durations when compared to the other 5 patients (52.8 months vs. 11.8 months), but it was not statistically significant. In conclusion, the detection and the localization of HBV antigen and DNA in renal tissues indicate the presence of the complete virion in the kidney. These results suggest that HBV may infect the kidneys of HBV carriers with MPGN.

A Case of Acute Renal Failure Due to Ingestion of Silicon Compound / 대한신장학회잡지

Excessive exposure to several metallic elements is known to produce a variety of nephrotoxic syndromes such as glomerulonephritis, nephrotic syndrome, interstitial nephritis, structural and functional abnormalities of proximal tubule resembling the Fanconi's syndrome and acute tubular necrosis. Although the pulmonary toxicities of silicon are relatively well documented as a cause of silicoproteinosis and lung fibrosis after acute and chronic exposure to free silica(SiO2), but is little known about the nephrotoxicity of this trace element. Clinical manifestations of silicon nephropathy are similar to other heavy metal nephropathy as proteinuria, hematuria, active urinary sediments and renal failure. Diagnosis of silicon nephropathy is based on distinct exposure history to silica, variable degree of renal dysfunction and characteristic histologic findings such as cytoplasmic vacuoles and dense membrane-enclosed cytoplasmic bodies which is resembling lysosomes in proximal tubular cells. A 26-year-old man with ingestion of silicon compound(SiO2-NaOCO3) developed acute renal failure due to acute tubular necrosis. And he was recovered with conservative management to acute renal failure. So we report this case with a brief review of literature.

Clinical Significance of Myocardial Perfusion Imaging Using Oral Dipyridamole Thallium-201 SPECT in Coronary Artery Disease

The clinical utility of thallium-201 SPECT combined dwith pharmacologic vasodilation induced by oral dipyridamole as an alternatiove to intravenous dipyridamole was incestigated in 21 patients who had concomitant coronary arteriography. Tomographic images were assessed visually. Sensitivity & specificity for overall detection of coronary artery disease were 93.7% and 80% respectively. Sensitivity & specificity for identification of indevidual diseased vessels were 84.6% and 87.5% for the left anterior descending artery, 75% and 84.6% for the right coronary artery, 60% and 100% for the left circumflex artery, respecitively. Of the 26 patients unergoing thallium scintigraphy 11 patients(42.3%) had some adverse effects between 20 and 50 minutes after oral dipyrdamole ingestion, including headache(26.9%), chest pain(26.9%), electrocardiographic changes(19.2%), and nausea(11.5%). Intravenous aminophylline was used to resolve these adverse effects in 8 patients & most of the adverse effects were subsided within 10 minutes. There was no ventricular arrhythmias, myocardial infarctions or deaths. In conclusion, oral dipyridamole thallium-201 SPECT is safe and accurate test for the overall detection of coranary artery disease and identification of disease in individual arteries. Furthermore it is useful for determining the necessities of coronary reperfusion and prognstically stratiofying the patients with coronary artery disease.