In this study the expression of the MRP2, MRP3, MRP4, MRP5, and SMRP genes was measured using TaqMan real-time polymerase chain reaction (PCR) in 103 children with previously untreated acute lymphoblastic leukemia (ALL) (precursor B-cell ALL [B-ALL], n = 71; T-cell ALL [T-ALL], n = 32).
Real-time PCR results showed that expression level of MDR1 was significantly higher in AML whereas expression of DHFR, BCRP and Survivin was significantly higher in ALL patients.
The ABCB1 and ABCG2 gene expression levels were analyzed using real-time polymerase chain reaction in 61 patients diagnosed with ALL and 99 healthy donors as controls.
We found significantly lower expression of the reduced folate carrier (SLC19A1, an MTX uptake transporter) in E2A-PBX1 ALL, significantly higher expression of breast cancer resistance protein (ABCG2, an MTX efflux transporter) in TEL-AML1 ALL, and lower expression of FPGS (which catalyzes formation of MTXPG) in T-lineage ALL, consistent with lower MTXPG accumulation in these ALL subtypes.
Furthermore, the MTHFR 677TT associated with the ABCG2 421GT + TT variant more significantly reduced the risk of adult ALL (OR = 0.32; 95% CI 0.12-0.85).
This observation also confirmed that, as in de novo Ph1-positive ALL, both the P190 and P210 varieties of BCR-ABL mRNA are observed in ALL with late-appearing Ph1.
Overexpression of miR-17-92 blocked the induction of apoptosis upon oncogene inactivation in the MYC and RAS-driven but not in the BCR-ABL-driven ALL leukemia.
We identified prominent molecular features of BCR-ABL-positive adult ALL, which may be useful for developing novel therapeutic targets and prognostic markers in this disease.
We have now used the same technique, reverse transcription/polymerase chain reaction amplification of ABL-BCR transcripts, to study nine patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL); seven expressed the P190 and two the P210 type of BCR-ABL fusion protein.
Southern blot analysis revealed no rearrangement in Mbcr1, and direct sequencing of the PCR product confirmed it to be the ALL-type mbcr1 fusion mRNA with the first exon of the BCR gene fused to ABL exon a2.
We here report the frequency of TEL-AML1, E2A-PBX1, MLL-AF4, and BCR-ABL chimeric transcripts in 264 Iraqi children newly diagnosed with acute lymphoblastic leukemia (ALL), using FTA cards impregnated with bone marrow aspirate or whole blood.
Studies of neonatal blood spots demonstrated that, in the child diagnosed at five years, the ETV6/ABL1 fusion initiating the ALL originated prenatally.
In acute lymphoblastic leukemia, besides age and white cell count at diagnosis, the cytogenetic abnormalities t(9;22)/BCR-ABL and t(4;11)/MLL-AF4 are important prognostic markers and are often included in the treatment stratification of patients with adult acute lymphoblastic leukemia.
However, the threshold 70 WT1 copies/104 ABL copies post induction in childhood ALL did not show clinical significance for predicting prognosis (p=0.056).
This la-Ph, expressing an acute lymphoblastic leukemia (ALL)-type BCR/ABL transcript, produces a novel P180BCR/ABL fusion protein reflecting deletion of 174 bases (58 amino acids) encoded by the a2 exon of the ABL gene.
In all patients, normal and leukemic repopulating stem cells could successfully be separated prospectively, and notably, the size of the normal HSC compartment in ETV6-RUNX1 and P190 BCR-ABL1ALLs was found to be unaffected by the expansive leukemic stem cell population.
Two models of leukemia were used, one genetic (conditional alpha4 ablation of BCR-ABL1 [p210(+)] leukemia) and one pharmacological (anti-functional alpha4 antibody treatment of primary ALL).
We established a new human BCR-ABL-positive acute lymphoblastic leukemia (ALL) cell line, SK-9 with the T315I mutation, from the peripheral blood of a 36-year-old female patient.