**3.6 The blast transformation**

*Cytogenetics - Classical and Molecular Strategies for Analysing Heredity Material*

(in situ hybridization: FISH) or real-time PCR search for the Philadelphia chromosome is necessary to confirm the diagnosis of CML and to monitor progress under

*The Philadelphia chromosome can be masked because of the size of the translocated fragment which is* 

In onco-hematology, FISH provides a decisive complement to the diagnosis, the prognosis and monitoring of targeted therapies. In leukemia chronic myeloid this technique highlights the fusion of genes *BCR* and *ABL* which characterize the Philadelphia chromosome (Ph). FISH is particularly interesting in the cytogenetic monitoring of CML. In due to culture problems (low mitotic index and the quality of the metaphases poor according to European Leukemia Net 2009. This service is currently offered to patients with CML as part of the cytogenetic monitoring of

Variant translocations fall into two subgroups: Simple variants and complex variants; their definitions are based on the results of R, G banding and molecular biology. Although it is very common, it is quickly learned that the t(9;22) translocation is not pathognomonic for CML and it has several variants: the Ph1 (+) variants, the masked Ph1 chromosome and the Ph1 (−) variants. All chromosomes except Y are involved in the variant form of Ph1 especially chromosomes 3, 11, 12, 14 and 17 [8]. The variants can all be considered as complex translocations since the molecular genetic investigations of the supposed simple variants show that they involve at least three chromosomes and always the 9 and

certain anti-mitotic drugs (**Figure 2**)**.**

*FISH image of* BCR/ABL *positive rearranged metaphase.*

their disease (**Figure 3**)**.**

**Figure 3.**

**Figure 2.**

*submicroscopic.*

**3.5 Variant translocations**

**132**

the 22 [9].

In this phase, 65 to 80% of patients develop additional chromosomal aberrations not due to chance which precede clinical and hematological manifestations by several months and which can serve as indicators prognosis [10, 11]. Secondary anomalies appear: Double chromosome Philadelphia, trisomy 8, isochromosome 17 and trisomy 19. These four additional abnormalities are part of the clonal course in 70% of CML Other, more rarely encountered anomalies seem to be due to chance, thus taking the minor pathways. In more than 50% of cases, they are represented by:


A quarter of patients [10, 11] will not develop any additional abnormalities and will keep Philadelphia alone for the duration of their survival.

## **3.7 Chronic myeloid leukemia with secondary abnormalities**

The following partial karyotypes show the association of certain additional abnormalities to the Philadelphia chromosome (Ph1) in our patients. However, the therapeutic and prognostic approach is totally different. It is therefore necessary:

Make a positive diagnosis for CML.


During the blast phase of CML at Ph1 (+), analysis determines as a factor of poor prognosis [10]. As for the Philadelphia chromosome alone, it appears to have an independent prognostic value [13].
