Blastic phase of chronic myelogenous leukemia

Abstract

Chronic myelogenous leukemia (CML), also known as chronic myelocytic or chronic myeloid leukemia, is a clonal disorder of hematopoiesis that arises in a hematopoietic stem cell or early progenitor cell. This is characterized by the dysregulated production of mature nonlymphoid cells with normal differentiation. Eventually, in spite of the term chronic, there is progression to acute leukemia, usually of the myeloid variety, which is highly resistant to current therapies. Despite recent improvements in the treatment of early-stage disease, CML blast crisis (CMLBC) remains a therapeutic challenge. CMLBC is highly refractory to standard induction chemotherapy, with a response rate in myeloid blast crisis of less than 30%. Conventional chemotherapy has been much less successful in this disease compared with de novo acute leukemia, with a mean survival after diagnosis of blast crisis of only 2 to 4 months for nonresponders. Many regimens of chemotherapies have been tried in CMLBC, with minor success. Although imatinib was evaluated in patients with CMLBC, most CMLBC cases today arise in patients already on imatinib-based therapy and developing blastic phase on that therapy; thus there is no standard therapy for patients with CMLBC. Further studies of the mechanisms of transformation of chronic-phase CMLBC at a molecular level, and methods to target these molecular abnormalities, will determine the future direction of new treatment modalities. The prognosis of CML in blast crisis remains disappointing, despite great efforts. Currently, the most successful strategy for improving survival in CML is by prolonging the chronic phase and delaying the onset of blast crisis.

Imatinib increases apoptosis index through modulation of survivin subcellular localization in the blast phase of CML cells

“…Patients in the chronic myeloid leukemia (CML) blast phase are highly refractory to treatment [1,2]. One of the most important imatinib resistance mechanisms in the CML is the inability of the Bcr-Abl CML cells to undergo apoptosis, which is caused by the BCR-ABL mutations decreasing the affinity of imatinib binding [3].…”

Monocytic Crisis of Chronic Myeloid Leukemia in the Era of Tyrosine Kinase Inhibitor

“…22 With the transition from CML chronic phase to blast crisis, 60% to 80% of patients acquire chromosomal changes in addition to the Ph chromosome. 23 The most common changes include double Ph chromosome, trisomy 8, trisomy 19, and isochromosome 17. 23 Previous cases of monocytic crisis also showed chromosomal abnormalities involving chromosomes 8, 19, and 22, as observed in the present case ; however, these abnormalities are not specifically restricted to monocytic crisis.…”

“…23 The most common changes include double Ph chromosome, trisomy 8, trisomy 19, and isochromosome 17. 23 Previous cases of monocytic crisis also showed chromosomal abnormalities involving chromosomes 8, 19, and 22, as observed in the present case ; however, these abnormalities are not specifically restricted to monocytic crisis. Of interest, the karyotype at the time of blast crisis was quite different from that during the accelerated phase in the present patient (Fig.…”

Gadd45a deficiency accelerates BCR-ABL driven chronic myelogenous leukemia

“…However, a substantial number of patients relapse due to development of resistance to imatinib therapy that leads to CML-BC, which is invariably fatal within weeks to months [24]. Thus, identification of additional genetic aberrations that play a role in the progression of CML is of utmost importance from a therapeutic point of view.…”