In conclusion we demonstrated that cells with the

In conclusion, we demonstrated that fexofenadine hydrochloride Supplier with the standard Ph had no detectable BCR–ABL1 KD mutations and that they were responsive to imatinib therapy, while cells with the variant translocation harbored two KD mutations, a previously described one and a never previously reported one [5]. These cells were resistant to imatinib, and in our case they were associated with the transformation to blast phase with karyotype evolution.
Introduction Chronic myeloid leukemia (CML) is a clonal malignant disorder of a pluripotent hematopoietic stem cell characterized by the presence of the reciprocal translocation t(9;22)(q34;q11), which generates the Philadelphia (Ph) chromosome. Frequency of additional chromosomal abnormalities has an incidence of 7% in chronic phase and increases to 40–70% in advanced disease/blast crisis [1,2]. Progression from chronic phase to accelerated phase or blast crisis is often associated with secondary chromosomal aberrations such as trisomy 8, trisomy 19, duplication of the Ph chromosome, isochromosome 17q (leading to the loss of p53 gene on 17p), acquisition of t(1;21) or translocations and inversions associated with AML/myelodysplasia [3], which translates a genomic instability of CML cells and the appearance of BCR-ABL1 kinase mutations, both of which can confer resistance to tyrosine kinase inhibitors (TKIs) [4,5].
Case report Genetic testing for Philadelphia chromosome was done by fluorescence in situ hybridization (FISH) and conventional cytogenetic analysis (karyotyping). The BCR-ABL fusion gene was assessed by RT-PCR. BCR-ABL rearrangement was detected by FISH in 96% of the bone marrow cell population and monosomy 7 in 71% of them (Fig. 1A and B). Cytogenetic features were as follows: 45,XX,-7,t(9;22)(q34;q11.2)[20] (Fig. 2A). The number of BCR-ABL transcripts at diagnosis was 70%. The patient received chemotherapy based on anthracycline, vincristine and steroids and imatinib at doses of 600mg daily with intrathecal chemotherapy, achieving complete remission of acute leukemia and chronic phase regression. Immediately after treatment, a new FISH assay in peripheral blood was performed and showed BCR-ABL rearrangement in 92% of cells, while monosomy 7 was not detected (Fig. 1C and D). Karyotype at that time was 46,XX,t(1;6),t(9;22)(q34;q11.2)[10]/46,XX[10]. Afterwards, the patient received consolidation therapy with vincristine and daunomycin plus imatinib, which was tapered to 400mg daily due to dyspnea and marked palpebral and ankle edema. Overall, she showed a good clinical outcome with 3.3% bcr-abl transcripts three months after diagnosis. Nevertheless, one week after this last determination, the patient returned to consultation due to headache and B symptoms. WBC showed leukocytosis of 258×109/L with 87% blasts. A new bone marrow had infiltration by 75% blasts of myeloid lineage consistent with myeloid blast crisis of CML. Immunophenotype of this blastic population was CD45+ CD34+d CD117+d DR+ CD38+ CD13+ CD33+ CD11b− CD64− CD56− CD7+/− CD9+d CD123+ showing the following karyotypic changes: 46,XX,t(1;6)(q22;q21),del(4)(p14),t(9;22)(q34;q11.2),der(11)add(11)(p14)add(11)(q23),add(17)(q12~21)[20] (Fig. 2B). The patient also developed a T315I bcr-abl mutation detected by DNA sequencing.
Discussion Thus, treatment for acute lymphoblastic leukemia based on chemotherapy and imatinib successfully erradicated the clone involved in lymphoblastic blast crisis while allowing a clonal selection and subsequent expansion of myeloid cells carrying the t(1;6). Very few cases of lineage switch in CML have been reported in the literature before [6–9] and during the imatinib era [10]. Furthermore, to our knowledge, this is the first report describing sequential lymphoid and myeloid blast crisis with differentiated cytogenetic abnormalities.
Introduction Haemoglobin Ypsilanti is a rare high oxygen affinity haemoglobin variant. The haemoglobinopathia is inherited autosomally dominant and most affected individuals are heterozygote. Due to the high oxygen affinity of the haemoglobin (Hb) molecule, hypoxia arises in the tissues, and secondary erythrocytosis develops [1].