Prevention of Blastic Crisis in Ph1-Positive Chronic Myeloid Leukemia

Abstract JunB is a component of the Jun family genes of the activating protein-1 transcription factors that are important in the control of cell growth and differentiation and neoplastic transformation. Recently, it was demonstrated that transgenic mice specifically lacking JunB expression in the myeloid lineage developed a myeloproliferative disease, eventually progressing to blast crisis that resembled human chronic myeloid leukemia (CML). To gain further insights into the role of JunB in human CML, we examined peripheral blood from 17 healthy individuals and CML patients (11 in blastic crisis and 21 in chronic phase) by real-time quantitative reverse transcription–polymerase chain reaction analysis for the expression of JunB. The results showed the expression levels of JunB were significantly impaired in CML cases (blastic crisis < chronic phase < normal). Mutational analysis of the whole gene and methylation analysis of cytosine-phosphate guanosine (CpG) sites at the promoter area were further performed to investigate the possible mechanisms. However, no mutation was found within the coding region or the 9 flanking evolutionarily conserved regions in all CML cases. Interestingly, in the promoter area of JunB gene, most of the CpG sites were methylated in CML cases; in contrast, none of these CpG sites were methylated in normal cases. Demethylation by treatment of hypermethylated K562 cells with 5′-aza-2′-deoxycytidine resulted in partial reactivation of JunB expression. Our results suggest that the down-regulated JunB expression in CML was due to the inactivation of JunB gene by methylation and the differential expression was correlated to the ratio of cells being methylated.

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Different Kinetic Pattern of Chronic Myeloid Leukemia: Lymphoblastic and Myeloblastic Blastic Crisis

Tumori Journal ◽

10.1177/030089168006600303 ◽

1980 ◽

Vol 66 (3) ◽

pp. 295-303

Author(s):

Wanda Piacibello ◽

Massimo Aglietta ◽

Felice Gavosto

Keyword(s):

Bone Marrow ◽

Acute Lymphoblastic Leukemia ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Lymphoblastic Leukemia ◽

Kinetic Studies ◽

Leukemic Cells ◽

Cell Kinetic ◽

Blastic Crisis ◽

Kinetic Pattern

Cell kinetic studies were performed in 8 ease of lymphoid blastic crisis (BC) of chronic myeloid leukemia at the onset of BC and during subsequent relapses. The results were compared with those found in 7 myeloblastic BC. While in the myeloblastic transformation the labeling index (LI) was always higher in bone marrow than in peripheral blood blasts, suggesting a predominant bone marrow proliferation of the leukemic cells, in the lymphoid transformation a higher LI was often found in peripheral blasts. Moreover, the lymphoblastic transformations were frequently characterized by lymphadenopathy. These findings point to the similarities between lymphoid BC and acute lymphoblastic leukemia, suggesting the possibility that a blastic event may originate in an extramedullary site and that an extramedullary BC is more likely to be lymphoid in nature.

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Imatinib mesylate as first-line therapy in patients with chronic myeloid leukemia in accelerated phase and blastic crisis: A retrospective analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.15_suppl.6569 ◽

2011 ◽

Vol 29 (15_suppl) ◽

pp. 6569-6569

Author(s):

N. K. Thota ◽

S. Gundeti ◽

P. Coca ◽

J. Srirambhatla ◽

R. Parimkayala ◽

...

Keyword(s):

Chronic Myeloid Leukemia ◽

Retrospective Analysis ◽

Imatinib Mesylate ◽

Myeloid Leukemia ◽

First Line ◽

Blastic Crisis ◽

First Line Therapy ◽

Line Therapy

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Presence of Three Philadelphia Chromosomes (Ph1) in the Blastic Crisis of a Case of Chronic Myeloid Leukemia

Tumori Journal ◽

10.1177/030089166705300402 ◽

1967 ◽

Vol 53 (4) ◽

pp. 315-321 ◽

Cited By ~ 3

Author(s):

Luigi Pegoraro ◽

Alessandro Pileri ◽

Giovanni Rovera ◽

Felice Gavosto

Keyword(s):

Alkaline Phosphatase ◽

Chronic Myeloid Leukemia ◽

Myeloid Leukemia ◽

Bone Marrow Cells ◽

Genetic Material ◽

Chromosome 21 ◽

Blastic Crisis ◽

Leukocyte Alkaline Phosphatase ◽

Random Expectation ◽

Two Parameters

Three Philadelphia chromosomes in addition to other extra-chromosomes in most of the bone marrow cells (70%) were observed in the terminal course of a case of chronic myeloid leukemia with blastic crisis. The percentage distribution of extra-chromosomes in the single groups of the Denver system was evaluated and compared with the theoretical expectation. This analysis showed a distribution of extra-chromosomes widely different from the random expectation, several chromosome groups being highly underrepresented (namely A, B, D and E) and others (C, F and G) overrepresented. From the karyotype analysis the commonest feature (27,4%) appeared to be the presence of three extra-chromosomes in group C, one extra in group F, and two extra Ph1 in group G. The leukocyte alkaline phosphatase performed on smears of peripheral blood gave a total value higher than normal. Various workers have connected the low values usually observed in chronic myeloid leukemia with the loss in chromosome 21 genetic material. In the present case, the increase in leukocyte alkaline phosphatase alongside an increase in chromatin 21 material might suggest a correlation between these two parameters.

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