| المساهمون: |
Baccarani, M., Iacobucci, I., Chiaretti, S., Foà, R., Balasubramanian, P., Paietta, E., Foroni, L., Jeromin, S., Izzo, B., Spinelli, O., Varma, N., Menif, S., Terragna, C., Seth, T., Bidet, A., Coriu, D., Lunghi, F., Mayer, J., Burt, E., Candoni, A., Albano, F., Luppi, M., Zupan, I., Lion, T., Zadro, R, Di Raimondo, F., Poopak, B., Rege-Cambrin, G., Annunziata, M., Ayala, A., Salinas-Viedma, V., Ines Prado, A., Milner, B., Galimberti, S., Janssen, J., Polli, V., Comba, L., Borsellino, B., Annibali, O., Crugnola, M., Passamonti, F. |
| الوصف: |
Philadelphia-chromosome positive (Ph+), BCR-ABL1+ acute lymphoblastic leukemia (ALL) is a distinct entity that is characterized by specific genomic alterations, low sensitivity to chemotherapy, unstable responsiveness to tyrosine kinase inhibitors (TKIs), and a poor prognosis [1–3]. The frequency of Ph+ ALL varies with age, ranging from <10% in children to about 50% in the elderly [3, 4]. Ph+ ALL is driven by a reciprocal translocation between chromosome 9 and chromosome 22, leading to the formation of hybrid fusion genes, that are all leukemogenic but can vary depending on the site of the breakpoints [5, 6]. The most common gene, that accounts for about 70–80% of all cases, results from the fusion of BCR exon 1 on chromosome 22 with ABL1 exon 2 on chromosome 9, much more rarely with ABL1 exon 3. The resulting e1a2 (or e1a3) fusion gene codes for a leukemogenic protein of 185–190 kd (P190). In 20–30% of cases, the breakpoint on chromosome 22 is downstream to BCR exon 1, resulting from the fusion of ABL1 exon 2 on chromosome 9 with either BCR exon 13 or BCR exon 14 on chromosome 22. The resulting fusion transcripts are named e13a2 (also known as b2a2), and e14a2 (also known as B3A2), respectively. The fusion e13a2 can give rise to only one transcript (e13a2) and one leukemogenic protein of 210 kd (P210). The fusion e14a2 usually give rise to one transcript (e14a2) that is longer, and codes for a leukemogenic protein that is also called P210, but has 25 additional amino acids and different secondary structure elements [5, 6]. Sometimes the e14a2 fusion gene, that retains BCR exon 13, can also generate a minor amount of e13a2 transcript, because of alternative splicing mechanisms. Therefore, the BCR-ABL1P210+ leukemias have two different molecular signatures:e13a2, and e14a2 (+_e13a2). The frequency of the two signatures has never been systematically investigated. In a paper from the MD Anderson Cancer Center it was reported that of 17 patients with Ph+, BCR-ABL1P210+ 76% expressed e13a2 [7]. In a previous ... |