Rapid diagnosis of mixed phenotype acute leukemia after identifying a blood histogram abnormality

A 38-year-old woman was suffering from back, right arm, and ankle joint pain, and visited our emergency department. Upon admission, the white blood cell (WBC) count was high (11,700/µL), and low numbers of red blood cells (2.21 × 106/µL) and platelets (PLTs) (42,000/µL) were observed. A PLT histogram showed an abnormally shaped peak at around 20–30 fL, suggesting the presence of giant PLTs or PLT aggregation. The WBC histogram showed abnormal elevation at 35 fL and around 100 fL, suggesting abnormal cells including nucleated red blood cells. A peripheral blood smear was prepared, and morphology was examined. As a result, blasts (4%) including many orthochromatic erythroblasts (48/100 WBCs) were observed. Acute leukemia was suspected, and the patient was transferred the next day to a hospital with a hematology department. Bone marrow aspiration revealed that 99% of cells were blasts positive for B lymphoid lineage markers and myeloperoxidase. The patient was diagnosed with mixed phenotype lineage acute leukemia, treated immediately, and achieved remission. Thus, careful observation of histogram abnormalities of an automatic blood cell analyzer is important for rapid diagnosis of acute leukemia. Keywords: Mixed phenotype acute leukemia, Automatic blood cell analyzer, Histogra

Molecular Defects of Uroporphyrinogen Decarboxylase in a Patient with Mild Hepatoerythropoietic Porphyria

The molecular defect of uroporphyrinogen decarboxylase (UROD) was examined in a patient with mild hepato- erythropoietic porphyria. To elucidate the UROD defect, we cloned UROD cDNAs from EBV-transformed lympho- blastoid cells of the proband using reverse transcriptase-polymerase chain reaction. Nucleotide sequence analysis of the cloned UROD cDNAs revealed two separate missense mutations, each occurring in a separate allele. One mutation was a Val134 → Gin transition, and was due to three sequential point mutations (T417G418T419 → CCA); the other mutation was a His220 → Pro transition (A677→ C). UROD pheno- type studies demonstrated that the TGT → CCA mutation was inherited from the father, and the A → C mutation was inherited from the mother. In contrast to the null activity previously described for a mutant UROD from a patient with familial porphyria cutanea tarda, these mutant URODs had subnormal but substantial enzyme activities, when expressed in Chinese hamster ovary cells. This is the first demonstration of a mutation caused by three sequential base substitutions