Mouse Anti-Synthetic abl Oncogene Peptide Hybridoma [421-30G8]

Ph+ chronic myeloid leukemia (CML) is a clonal myeloproliferative disease whose clinical course is characterized by progression disease from the early chronic phase (CP) to the fatal blastic phase (BP). This programmed course is closely related to the translocation t(9;22)(q22;q11) and the resulting BCR-ABL1 fusion protein (p210) that drives the leukemic transformation of hematopoietic stem cells. Therefore, the cure of CML can only pass through the abrogation of the Ph+ clone. Allogeneic stem cell transplantation (allo-SCT) and interferon-alpha (IFN alpha) have been proven to reduce the Ph+ clone in a limited proportion of CML population and this translated in a lower rate of progression to BP and in a significant prolongation of survival. Tyrosine-kinase inhibitors (TKIs), lastly introduced in 2000, by preventing the disease blastic transformation and significantly prolonging the survival in up to 90% of the patient population, radically changed the fate of CML. The current therapy with TKIs induces a chronicization of the disease but several criticisms still persist, and the most relevant one is the sustainability of long-term therapy with TKIs in terms of compliance, toxicity and costs. The perspectives concern the optimization of therapy according to the age, the risk of disease, the potency and the safety profiles of the TKIs. The prolongation of survival is the most important end point which should be guaranteed to all patients. The treatment free remission (TFR) is the new goal that we would like to give to an increasing number of patients. The cure remains the main objective of CML therapy.

BACKGROUND The Janus kinase 2 (JAK2) V617F mutation is common in patients with breakpoint cluster region-Abelsonl (BCR-ABL1)-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and primary myelofibrosis, but is rarely detected in BCR-ABL1-positive chronic myeloid leukemia (CML) patients. Here, we report a CML patient with both a BCR-ABL1 rearrangement and JAK2 V617F mutation. CASE SUMMARY A 45-year-old Chinese woman was admitted to our department with a history of significant thrombocytosis for 20 d. Color Doppler ultrasound examination showed mild splenomegaly. Bone marrow aspiration revealed a karyotype of 46, XX, t(9;22)(q34;q11.2) in 20/20 metaphases by cytogenetic analysis, rearrangement of BCR-ABL1 (32.31%) by fluorescent polymerase chain reaction (PCR) and mutation of JAK2 V617F (10%) by PCR and Sanger DNA sequencing. The patient was diagnosed with CML and JAK2 V617F mutation. Following treatment with imatinib for 3 mo, the patient had an optimal response and BCR-ABL1 (IS) was 0.143%, while the mutation rate of JAK2 V617F rose to 15%. CONCLUSION Emphasis should be placed on the detection of JAK2 mutation when CML is diagnosed to distinguish JAK2 mutation-positive CML and formulate treatment strategies.