Hui-Jen Tsai

Altered expression of circadian clock genes in human chronic myeloid leukemia.

Circadian clock genes use transcriptional-translational feedback loops to control circadian rhythms. Recent studies have demonstrated that expression of some circadian clock genes displays daily oscillation in peripheral tissues including peripheral blood and bone marrow. Circadian rhythms regulate various functions of human body, and the disruption of circadian rhythm has been associated with cancer development and tumor progression. However, the direct links between aberrant circadian clock gene expression and human disorders remain largely unknown. In this study, comparisons were made between the expression profiles of 9 circadian clock genes from peripheral blood mononuclear cells (PBMCs) and polymorphonuclear cells (PMNs) from 18 healthy volunteers. Peripheral blood (PB) total leukocytes from 54 healthy volunteers and 95 patients with chronic myeloid leukemia (CML) were also investigated. Similar expression profiles of all 9 circadian clock genes were observed in PBMCs and PMNs of healthy individuals. In PB total leukocytes of healthy individuals, the daily pattern of PER1, PER2, PER3, CRY1, CRY2, and CKIε expression level peaked at 0800 h, and BMAL1 peaked at 2000 h. Daily pattern expression of these 7 genes was disrupted in newly diagnosed pre—imatinib mesylate—treated and blast crisis—phase patients with CML. Partial daily pattern gene expression recoveries were observed in patients with CML with complete cytogenetic response and major molecular response. The expression of CLOCK and TIM did not show a time-dependent variation among the healthy and patients with CML. These results indicate a possible association of the disrupted daily patterns of circadian clock gene expression with the pathogenesis of CML.

PCR-Based Analysis of α-Thalassemia in Southern Taiwan

The Southeast Asia type deletion of α-thalassemia-1 (--sea) is the most common type of α-thalassemia-1 in Taiwan. There are 2 less common types, Filipino type (--fil) and Thai type (--thai). In the current study, we screened 754 cases of α-thalassemia-1 in Southern Taiwan using a polymerase chain reaction (PCR)-based method. Our results show that the prevalence of the (--sea) type is 90.6%, followed by the (--fil) type (8.6%), the (--thai) type (0.5%), and the (-α3.7/-α3.7) type (0.3%). We also analyzed the genotypes of 96 patients with hemoglobin (Hb) H disease and 48 cases of hydrops fetalis with Hb Bart’s. The frequencies of the genotypes of the α-thalassemia-1 allele in Hb H disease are in accordance with the results of analyses of α-thalassemia-1 cases. The α-thalassemia-2 allele includes -α3.7, -α4.2,-αG, αCSα, and αQSα. Forty-one cases, 6 cases, and 1 case of hydrops fetalis with Hb Bart’s were caused by --sea/--sea, --sea/--fil, and--sea/--thai, respectively. The genotypes and frequencies of α-thalassemia in this study are different from those in previous studies in Taiwan and Hong Kong. These differences may be attributed to the diverse genetic origin among different ethnic groups and the extensive inclusion of the (--fil) and (--thai) α-thalassemia-1 types.

Additional chromosome abnormalities in chronic myeloid leukemia

The Philadelphia (Ph) chromosome and/or Breakpoint cluster region‐Abelson leukemia virus oncogene transcript are unique markers for chronic myeloid leukemia (CML). However, CML demonstrates heterogeneous presentations and outcomes. We analyzed the cytogenetic and molecular results of CML patients to evaluate their correlation with clinical presentations and outcome. A total of 84 newly diagnosed CML patients were enrolled in the study. Patients were treated according to disease status. Bone marrow samples were obtained to perform cytogenetic and molecular studies. Clinical presentations, treatment courses, and survival were reviewed retrospectively. Among 84 patients, 72 had chronic phase and 12 had accelerated phase CML. Cytogenetic study showed 69 (82.1%) with the classic Ph chromosome, 6 (7.2%) with a variant Ph chromosome, and 9 (10.7%) with additional chromosome abnormalities. Fifty‐four (64.3%) cases harbored b3a2 transcripts, 29 (34.5%) had b2a2 transcript, and 1 had e19a2 transcript. There was no difference in clinical presentations between different cytogenetic and molecular groups; however, additional chromosome abnormalities were significantly associated with the accelerated phase. Imatinib therapy was an effective treatment, as measured by cytogenetic response, when administered as first‐ and second‐line therapy in chronic phase patients. Survival analysis showed that old age, additional chromosome abnormalities, high Sokal score, and no cytogenetic response in second‐line therapy had a significant poor impact (p < 0.05). In conclusion, we presented the cytogenetic and molecular pattern of CML patients and demonstrated that the additional chromosome abnormality was associated with poor outcome.

A RARE CASE OF COMBINED SMALL-CELL LUNG CANCER WITH UNUSUAL SOFT TISSUE METASTASIS

Combined small‐cell lung carcinoma (SCLC) is a rare tumor. We report a case of combined SCLC of the lung, including adenocarcinoma and spindle‐shaped cell tumor, with an unusual initial presentation. The patient suffered from a right shoulder mass, subsequently undergoing biopsy. A lung nodule was noted later after complete examination. The diagnosis turned out to be combined cell carcinoma with three different components (small‐cell carcinoma, adenocarcinoma, and spindle‐shaped cell tumor) after examination upon total removal of the lung nodule by lobectomy. In addition to the rarity of the three components in such a tumor, soft tissue metastasis also made it an unusual case.

Pure Red Cell Aplasia After ABO Major-Mismatched Allogeneic Peripheral Blood Stem Cell Transplantation Successfully Treated with Plasma Exchange and Low-Dose Steroid: Two Case Reports

Pure red cell aplasia (PRCA) is a complication of ABO‐incompatible allogeneic stem cell transplantation. The mechanism is not well known, although the isoagglutinin titer before transplantation or cyclosporine use is considered to be the cause. Patients with this complication require more blood transfusions than those without it. There is no standard treatment. We report two cases of PRCA after allogeneic peripheral blood stem cell transplantation that were successfully treated with plasma exchange and low‐dose steroid.

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.

Invasive Fungal Infections in Patients with Acute Leukemia

Invasive fungal infections, a serious problem among cancer patients, are increasing in incidence, and can cause morbidity and mortality. Such infections may hinder additional treatment, especially for patients with leukemia. We report here our experiences in the management of invasive fungal infection in patients with acute leukemia. A total of 18 patients were enrolled in the study: 12 had microabscesses of the liver and/or spleen and/or kidneys; four had sinonasal infections; and two had pulmonary infections. Most of the patients (88.9%) received amphotericin B during treatment for fungal infection. Thirteen patients achieved complete response without evidence of fungal infection in follow‐up. In the study, there were 11 mortalities, including five patients who died during therapy and six who later died as a result of relapse or refractoriness of the leukemia. We suggest that many patients may have a good response to antifungal therapy, and that fungal infection does not have to preclude additional chemotherapy after proper management. The state of the underlying disease has a strong impact on outcome.

Immunoprofiles in malignant peripheral nerve sheath tumor: three case reports and literature review.

Because there are no standardized radiologic and histologic criteria, the differential diagnosis of malignant peripheral nerve sheath tumors (MPNSTs) from other spindle cell neoplasms poses great challenges for pathologists. Because early diagnosis of MPNSTs arising from benign peripheral nerve sheath tumors (BPNSTs) means a better prognosis, many immunohistochemical and molecular studies have recently emerged. Nevertheless, no gold standard diagnostic criterion is to be found in the literature. For example, S‐100 protein is widely used in the diagnosis of MPNST. Other promising ancillary markers are p53 and Ki‐67; however, the staining patterns and possible mechanisms of these markers are seldom mentioned in the literature. These evoke our interest. Only six cases diagnosed as MPNST were retrieved from the archives of the Department of Pathology, Kaohsiung Medical University Chung‐Ho Memorial Hospital between 1988 and September 2005. Clinical files were available for three of them, and we found nuances in the immunohistochemistry from these previous reports. Here, we present these rare sarcomas and review the literature.

Poor Outcomes in Patients with Primary Malignant Mediastinal Germ-cell Tumors

Primary mediastinal germ‐cell tumors (GCTs) without gonadal involvement are rare and can be divided into benign mature teratoma and malignant seminoma or nonseminoma. We describe our experience of malignant mediastinal GCTs and compare the presentations and outcome with those of benign teratomas. Four malignant GCTs (1 seminoma, 1 choriocarcinoma, and 2 yolk‐sac tumors) have been treated in our hospital. All patients were men with obvious symptoms before diagnosis. The patient with seminoma was treated with surgery and radiation, while those with nonseminoma tumors were treated with chemotherapy and/or surgery. Two patients died, one with extended pulmonary metastasis and the other with relapsed disease and high levels of tumor markers. Compared with the nine cases of benign teratomas, the four malignant GCTs showed overwhelming male dominance, advanced symptoms at presentation, and poor outcome. These cases highlight the important role of disease staging and tumor‐marker levels in malignant GCTs, and suggest that new treatment strategies for malignant GCTs await further investigation.