Chronic myeloproliferative diseases with and without the Ph chromosome: some unresolved issues

Differential expression of JAK2 and Src kinase genes in response to hydroxyurea treatment in polycythemia vera and essential thrombocythemia

“…[3] Despite the fact that JAK2 V617F has facilitated the diagnosis of MPN, and improved our knowledge on their pathogenesis, there are still a number of unanswered questions. [4] Although formerly believed to be a single-step process, recent evidence has shown that the JAK2 V617F mutation is neither the sole, nor sufficient molecular event, responsible for MPN. It may also not be the initial one, and other somatic mutations may precede JAK2…”

Dual inhibition of Jak2 and STAT5 enhances killing of myeloproliferative neoplasia cells

“…4 Although small molecule Jak2 inhibitors are entering clinical trials, their ultimate efficacy is unclear. 5 In addition to the concern of insufficient inhibition of mutated Jak2 in vivo or the emergence of resistance through activation of complementary pathways, many MPNs contain other mutational events (for example, mutation in exon12 of Mpl, 6 or the KIT D618V mutation in patients with systemic mastocytosis 7 ), and thus are not sensitive to Jak inhibitors. Therefore, the development of inhibitors to common mediators of diverse signaling pathways in this disease is very desirable.…”

Analysis of BCR/ABL transcripts in healthy individuals

“…The expression of BCR/ABL results in the formation of chimeric proteins with abnormal tyrosine kinase activity, p210 BCR/ABL , which exert oncogenic effects throughout the course of the disease (Saglio et al, 1996;Kurzrock et al, 2003). BCR/ABL proteins lead to an unbalanced cell cycle, increasing the activity of tyrosine kinase, and continuing the cycle even in the absence of growth factors (Di Bacco et al, 2000;Fernandes-Luma, 2000;Goldman et al, 2009).…”