A total of 11 children (five males and six females) with hypergranular type of acute promyelocytic leukemia (APML) were treated with intravenous arsenic trioxide (As 2 O 3 ) between December 1998 and October 2003. Eight cycles of As 2 O 3 (0.15 mg/kg/day) were administered (induction, consolidation and six cycles of maintenance) over a period of 12 months. The median WBC count at diagnosis was 3400/mm 3 (range: 800-9800). In all, 10 patients (91%) achieved hematological remission at a mean duration of 48 days (range: 41-60) with all 10 patients achieving molecular remission at a median duration of 81 days (range: 64-109). Toxicity was minimal with leukocytosis in six patients, ichthyosis and hyperpigmentation of skin in five and mild peripheral neuropathy in one patient. One patient who relapsed 6 months after completing therapy achieved a second hematological and molecular remission with As 2 O 3 . With a median follow-up of 30 months (range: 4-62), the overall (OS) survival is 91% with a relapse-free survival (RFS) of 81%. As 2 O 3 achieves hematological and molecular remission in majority of newly diagnosed children with APML with minimal toxicity, but long-term follow-up is required to evaluate late effects of As 2 O 3 and study the minimum dose and duration required for a sustained remission.

The frequency (1.7%) and distribution of these translocations in our series and the association with 1q and 13q abnormalities is similar to the literature. Trisomies 7 and 12 were seen in less than 10% of our patients.

Patients with acute promyelocytic leukemia (APML) with the t(11;17) translocation usually respond poorly to all-trans retinoic acid (ATRA) and chemotherapy. We describe a patient with promyelocytic leukemia zinc finger/retinoic acid receptor alpha (PLZF/RARalpha) APML who was treated with combination chemotherapy after poor response to arsenic trioxide. He achieved hematological remission in 4 weeks followed by achievement of molecular remission in 8 weeks. Four cycles of consolidation chemotherapy followed by four cycles of maintenance therapy were given over a period of 9 months. At a follow-up of 32 months after achieving hematological remission, he continues to remain in hematological and molecular remission with normal blood parameters and negative reverse transcriptase polymerase chain reaction (RT-PCR) results. Combination chemotherapy can achieve sustained remission in patients with PLZF/RARalpha APML.

The hypothesis was tested that sequence diversity in breast cancer resistance protein (BCRP)'s cis‐regulatory region is a significant determinant of BCRP expression. The BCRP promoter and intron 1 were resequenced in lymphoblast DNA from the polymorphism discovery resource (PDR) 44 subset. BCRP single nucleotide polymorphisms (SNPs) were genotyped in donor human livers, intestines, and lymphoblasts quantitatively phenotyped for BCRP mRNA expression. Carriers of the ‐15622C>T SNP had lower BCRP expression in multiple tissues. The intron 1 SNP 16702C>T was associated with high expression in livers; 1143G>A was associated with low expression in intestine; 12283T>C was associated with higher expression in the PDR44 and White livers. The ‐15994C>T promoter SNP was significantly associated with higher BCRP expression in multiple tissues. Patients with the ‐15994C>T genotype had substantially higher clearance of p.o. imatinib. Liver polymorphically expressed an alternatively spliced mRNA [splice variant (SV) 1] skipping exon 2. Although SV1+ livers did not uniformly carry the exon 2 G34A allele, 90% of G34A livers expressed SV1. BCRP mRNA was significantly lower among Hispanic livers with the G34A variant genotype and may be due, in part, to polymorphic exon 2 splicing. Allele expression imbalance and use of multiple promoters were seen in BCRP mRNA. In conclusion, BCRP expression in lymphoblasts, liver, and intestine is associated with novel promoter and intron 1 SNPs.

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