الفهرس 
CHRONIC MYELOID LEUKAEMIAOnly 14 pages are availabe for public view
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Abstract
Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by the presence of Philadelphia chromosome.
The other important risk factors are high doses of ionizing radiation, alcohol, obesity and occupational exposure to benzene.
The disease has three phases, chronic phase (CP), accelerated phase (AP) and blastic crisis (BC).
CML has a worldwide incidence of 1-1.5 cases per 100,000 inhabitants.
CML constitutes 15-20% of all leukemias.
The median age at diagnosis is 40-60 years.
CML incidence rates in western countries vary from 0.6 to 2 cases per 100,000 inhabitants
Reliable epidemiological information on chronic myeloproliferative disorders is rare.
Geographic and ethnic variations contribute to the variability of incidences among CML registries. (Oehler, 2013)
BCR-ABL gene codes for a protein tyrosine kinase (PTK) that is the recognized cause of the leukemic transformation of hematopoietic stem cells (Quintas-Cardama A and Cortes J.2009).
This hybrid gene is generated by a reciprocal translocation between chromosome 9 (ABL) and chromosome 22 (BCR), to a fusion gene that is located on chromosome 22 (Philadelphia chromosome). In CML, the breakpoints in chromosome 22 are located in major breakpoint cluster region (M-BCR), leading to origin to two transcripts, e14a2 (B3A2) or e13a2 (B2A2) coding for PTK of slightly different length (P210) (Melo J 1996). Much more rarely, the breakpoint is located outside the M-BCR, either in the minor BCR (mBCR), leading to a fusion gene (e1a2) that codes for a similar PTK (P190), the latter is more common in Ph+ acute lymphoblastic leukemia, or in the so called micro BCR (µBCR) leading to a fusion gene (e19a2) coding for another PTK (P230) that is the molecular marker of a neutrophilic variant of CML. (Quintas-Cardama A and Cortes J. 2009). Other, rare transcripts have also been reported. Therefore, more than 90% of CML are B3A2 or B2A2. Alternative splicing or mispricing of the primary transcript can lead to a contemporary expression of both transcripts (B3A2/B2A2), and sometimes also to a detectable co-expression of the e1a2 transcript (P190) (Melo J 1996).
Both B3A2 and B2A2 code for a protein (P210) with a TK function, but with a slightly different length (25 amino acids). It is not known if their activity is identical. It has been reported that they may affect the characteristics of the disease and the risk (Pfirrmann M, et al. 2017). It has not been found that they affect survival, but it has been reported that they affect the rate, the speed, and the depth of the molecular response to TKIs (Jain P, et al. 2016). Moreover, it has been reported that the two P210 may have a different immunogenicity, an important difference that may affect the probability of achieving a deep or a complete molecular remission ( Tarafdar A, et al. 2017).
The incidence of B3A2 and B2A2 has been reported in some studies ( Hanfstein B,et al.2014), but not in the majority of the studies of treatment with TKIs. It is not known if the incidence may be affected by ethnic, geographic, gender, and age variables. The incidence and the country, region, gender and age distribution of the so-called rare types are not known. Therefore, the true incidence of BCR-ABL transcript types is unknown. The definition of the incidence of the transcript type is a necessary prerequisite to any other study of the biologic and clinical value of the transcript type.
The results of the treatment of chronic phase (CP) Ph+ BCR-ABL1+ CML with TKIs are excellent, survival being very close to the survival of non-leukemic individuals (Baccarani M et al. 2013).
Therefore, there is little room for an improvement of survival. However, there is large room for an improvement of treatment-free remission (TFR), that is the major goal of current treatment (Baccarani M et al. 2013)..
The transcript type is important because it may affect the probability of achieving the deep molecular response that is required to achieve TFR (Baccarani M et al. 2013).