BCL6 expression correlates with the t(1;19) translocation in B-lymphoblastic leukemia.

OBJECTIVES: Study to date suggests that BCL6 protein expression in B-cell neoplasia predominates in germinal center-derived tumors, but less is known regarding its expression in B-lymphoblastic leukemia. Therefore, we designed a comprehensive study of BCL6 expression in B-lymphoblastic leukemia. METHODS: BCL6, LMO, and HGAL protein expression in B-lymphoblastic leukemia was investigated using immunohistochemical staining of paraffin-embedded bone marrow specimens. Cryptic TCF3(E2A)-PBX1 rearrangements were investigated using interphase fluorescence in situ hybridization. RESULTS: Six (12%) of 52 B-lymphoblastic leukemias demonstrated BCL6 protein expression, with B-cell lymphoblastic leukemias containing a t(1;19) translocation demonstrating the strongest staining (three of three). Additional t(1;19) cases beyond the screening study showed similar results. Public microarray expression database mining showed that BCL6 messenger RNA expression levels in B-lymphoblastic leukemia correlated with the protein expression findings. Finally, other markers of B-cell development correlated with BCL6 expression in t(1;19) B-lymphoblastic leukemia cases, with LMO2 and HGAL proteins expressed in six (67%) of nine and eight (89%) of nine cases, respectively. CONCLUSIONS: BCL6 expression is present in a subset of B-lymphoblastic leukemias, especially in cases containing the 1;19 translocation. Investigation for TCF3(E2A)-PBX1 rearrangements may be useful in BCL6-positive B-lymphoblastic leukemia.

Rituximab therapy for pure red cell aplasia due to anti-epoetin antibodies in a woman treated with epoetin-alfa: a case report.

INTRODUCTION: Pure red cell aplasia due to anti-epoetin antibodies is a known complication of epoetin therapy for anemia due to chronic kidney disease. This disease has not previously been well described in the setting of therapy for chronic hepatitis C virus infection. While treatment for pure red cell aplasia due to anti-epoetin antibodies is usually with immunosuppressive therapy such as calcineurin inhibition, the safety of this treatment in chronic hepatitis C virus infection is unknown. To date, little has been published on the efficacy of rituximab on pure red cell aplasia due to anti-epoetin antibodies. CASE PRESENTATION: This report describes a 65-year-old Asian-American woman who developed pure red cell aplasia from high titer neutralizing anti-epoetin antibodies after epoetin-alfa therapy during ribavirin and peg-interferon treatment for chronic hepatitis C virus infection. We describe the outcome of her treatment with rituximab. The reticulocyte count increased, and anti-epoetin antibody titer decreased with a loss of neutralizing activity in vitro, leading to a reduction in blood transfusions, and eventual resolution of anemia, without reactivation of hepatitis C virus. CONCLUSION: The diagnosis of pure red cell aplasia from anti-epoetin antibodies should be considered in patients undergoing therapy for chronic hepatitis C virus infection who develop severe anemia after administration of erythropoietin or darbepoetin. Though it is currently an off-label indication, rituximab is a therapeutic option for patients with pure red cell aplasia due to anti-epoetin antibodies.

Medulloblastoma simulating acute myeloid leukemia: case report with a review of "myeloid antigen" expression in nonhematopoietic tissues and tumors.

Medulloblastoma is a primitive neuroectodermal tumor arising in the posterior fossa usually in the first decade of life. Systemic metastases are infrequent at diagnosis and usually occur after surgical resection or shunt placement. We report a rare case of medulloblastoma in an 18-year-old woman who presented with headache, leukopenia, and anemia. Neurologic examination was normal. Bone marrow evaluation revealed primitive cells morphologically resembling blasts. By flow cytometry, these cells lacked CD45 and expressed CD13/33, CD15, CD34, HLA-DR, and strong CD56. The presence of myeloid antigens and CD34 suggested acute myeloid leukemia; however, the bone marrow core biopsy architecture and tumor cells in cerebrospinal fluid were more compatible with a nonhematopoietic tumor. Further workup revealed a cerebellar mass, and a diagnosis of desmoplastic medulloblastoma was made. To our knowledge, this is the first reported case of a nonhematopoietic small round blue-cell tumor expressing multiple myeloid antigens and CD34 by flow cytometry.

Acquired Pelger-Huët anomaly in association with concomitant tacrolimus and mycophenolate mofetil in a liver transplant patient: a case report and review of the literature.

Pelger-Huët anomaly is a congenital or acquired abnormality of neutrophil nuclear segmentation. The acquired form may be a result of a clonal myeloid malignancy, such as myelodysplastic syndrome, or may be a secondary nonclonal change related to a variety of underlying causes, including infections and medications. We report a case of a 56-year-old man who developed acquired Pelger-Huët anomaly following liver transplantation while on the immunosuppressive agents tacrolimus and mycophenolate mofetil. These medications have been reported in association with this abnormality, but usually as a single agent or in combination with other drugs. In our case, the Pelger-Huët anomaly may be the result of the combination of these 2 drugs or mycophenolate alone with subsequent desensitization because resolution of the abnormality occurred after a reduction in mycophenolate mofetil dose, and the abnormality did not recur when mycophenolate mofetil was increased to a dose previously associated with Pelger-Huët anomaly during the time that tacrolimus was discontinued.

Clinically relevant differences in prothrombin time and INR values related to blood sample collection in plastic vs glass tubes.

We compared prothrombin times (PTs) and international normalized ratios (INRs) for blood samples drawn into plastic vs glass collection tubes. We collected 60 venous blood samples into 4.5-mL glass and 2 plastic tubes (2.7 and 3.5 mL). An additional 153 samples, including 63 from warfarin-anticoagulated patients, were collected only in glass and 2.7-mL plastic tubes. The PTs and INRs were determined following routine laboratory procedures. A subset of 35 frozen aliquot samples was analyzed with a different instrument-reagent combination. The PTs and INRs for samples in plastic tubes were significantly lower than for samples in glass tubes. The mean INR differences increased with INR magnitude from approximately -0.1 (INR, 1.5) to -0.7 (INR, 4.5). Of the plastic tube INRs, 50% were more than 10% lower than INRs from samples collected in glass tubes. Therapeutic monitoring based on plastic-tube INRs could result in higher doses of warfarin.

Pediatric acute blastic natural killer cell leukemia.

The goal of this report is to describe a rare case of pediatric blastic natural killer (NK) cell leukemia and to compare pediatric blastic NK cell leukemia/lymphoma to other reported cases of pediatric NK cell leukemia. The patient, a 9-year-old girl, presented with acute leukemia with a phenotype similar to adult blastic NK cell leukemia/lymphoma. The blasts were agranular and expressed CD7, 45, 56, and HLA-DR, but not CD3, 11c, 13, 33, or TdT. She had a complete response to ALL-directed chemotherapy, but had multiple relapses involving the cerebrospinal fluid, nasal sinus, lymph node and skin. In addition to the reported case, a review of the literature identified 9 previously reported cases of NK cell leukemia in patients 18 years of age or less. Cases were subdivided into blastic, acute/aggressive, and myeloid precursor NK cell leukemia based upon CD13/33 expression and morphologic characteristics. Compared to pediatric acute/aggressive NK cell leukemia, children with blastic NK cell leukemia showed greater variation in age and race. Prognosis was poor for all groups. Pediatric blastic NK cell leukemia is a distinct clinicopathologic entity which differs from other types of pediatric NK cell leukemia.