**4. Prognostic interest of chromosome Philadelphia in CML**

Evaluating the prognosis of CML using clinical-biological criteria can predict the probable date of onset of blast transformation which amounts to determining the probable duration of the chronic phase. As regards the cytogenetic criterion, it must be defined and homogeneous. The prognoses of Ph1 (+) CML and Ph1 (−) CML should be studied separately because we have seen the current difficulties of including the Ph1 (−) form in the nosological framework of CML.

In our medical genetics' laboratory. The suspected diagnosis was CML in 69 patients, unlabeled SMP in the remaining 22 patients (**Table 1**).


The cytogenetic criterion is requested at two levels:


During the chronic phase of Ph1 (+) CML and without the knowledge of multiparametric analyzes, it has been shown that the most significant prognostic factors which determine the duration of survival are [14]:


#### **Table 1.**

*(a) Cytogenetic analysis in myeloproliferative syndromes 91 patients. (b) Frequency of the Philadelphia chromosome (Ph1).*

#### **Figure 4.**

*(a) Presence of an extra Ph1 chromosome and trisomy 21. (b) Partial trisomy 8. (c) Partial band karyotype RHG: T(9;X;22).*

**135**

**Table 2.**

*Research of the Philadelphia Chromosome in Chronic Myeloid Leukemia: Diagnostic…*

• A clonal evolution a \ double chromosome Ph1, a trisomy 8, and typical aberrations of the acute phase (Ph1 (+), i(17q), hypodiploidy or hyperdiploidy).

It is interesting to note that the double chromosome Ph1 or trisomy 8 are more frequent in acute transformations of the AML, ALL type and that they respond

Residual disease is defined as the number of malignant cells persisting after cytotoxic treatment, the eradicative action of which is intended to be as complete as possible: Chemotherapy, ionizing radiation, bone grafting. The residual malignant cells which escape this treatment can be the cause of a relapse hence the need to quantify them as precisely as possible. Before the introduction of molecular biology, hematologists had at their disposal various means of approach to define the biological remission of a hemopathy: Cytology, cytogenetics, immunology. In the best case, the sensitivity of these techniques did not make it possible to detect less than one residual cell in 100, a very insufficient sensitivity threshold to help clinician to decide for adequate treatment and to evaluate the quality control of the graft. The treatments envisaged must be carried out in order to obtain hematological remission and if possible a complete eradication of the Ph1 (+) cells (cytogenetic remission) with regard to chronic myeloid leukemia, the evolution takes place in two stages: A first chronic or myelocytic phase easily controlled by usual therapies then a second inconstant transition phase called acceleration with resistance to conventional chemotherapy, following which an acute transformation occurs, often of the terminal acute myelogenous leukemia type, constantly fatal, inevitable on average 3 to 4 years after diagnosis.

**6. Contribution of oncocytogenetics in chronic myeloid leukemia**

**Chromosomes RNAm Protein** 9 ARNm c-abl P145c−abl 22 ARNm bcr P160bcr 22q- ARNm bcr-abl P210bcr−abl

*The chromosomes involved and their molecular consequences.*

The molecular consequence is the formation of a *BCR-ABL* fusion gene, transcribed into 8.5 Kb mRNA and translated into 210 Kd protein with greater tyrosine kinase activity compared to the normal protein of the proto oncogene c-*ABL* from 145 Kb, this protein is involved in the pathological process of CML [15]. The molecular biology techniques applied to DNA, mRNA (RT-PCR) and encoded

*DOI: http://dx.doi.org/10.5772/intechopen.95865*

• Thrombocytopenia.

• Leukocytosis>20.109 / l.

• Non-lymphoid blast cells.

• Lack of response to treatment.

**5. Surveillance of residual disease**

poorly to treatment (**Figure 4**)**.**

*Research of the Philadelphia Chromosome in Chronic Myeloid Leukemia: Diagnostic… DOI: http://dx.doi.org/10.5772/intechopen.95865*

• Thrombocytopenia.

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

combination with baseline clinical and hematologic data.

• Then to assess the prognosis later during the blast transformation.

• For the initial assessment of prognosis at the time of diagnosis of CML in

During the chronic phase of Ph1 (+) CML and without the knowledge of multiparametric analyzes, it has been shown that the most significant prognostic factors

• The presence of additional clonal chromosomal abnormalities (relative risk

*(a) Presence of an extra Ph1 chromosome and trisomy 21. (b) Partial trisomy 8. (c) Partial band karyotype* 

*(a) Cytogenetic analysis in myeloproliferative syndromes 91 patients. (b) Frequency of the Philadelphia* 

The cytogenetic criterion is requested at two levels:

which determine the duration of survival are [14]:

• Circulating blasts greater than 5% "RR = 1.8".

• A hemoglobin rate of less than 10 g / dl "RR = 1.30".

"RR" = 4.5).

**134**

**Figure 4.**

**Table 1.**

*chromosome (Ph1).*

*RHG: T(9;X;22).*


It is interesting to note that the double chromosome Ph1 or trisomy 8 are more frequent in acute transformations of the AML, ALL type and that they respond poorly to treatment (**Figure 4**)**.**

## **5. Surveillance of residual disease**

Residual disease is defined as the number of malignant cells persisting after cytotoxic treatment, the eradicative action of which is intended to be as complete as possible: Chemotherapy, ionizing radiation, bone grafting. The residual malignant cells which escape this treatment can be the cause of a relapse hence the need to quantify them as precisely as possible. Before the introduction of molecular biology, hematologists had at their disposal various means of approach to define the biological remission of a hemopathy: Cytology, cytogenetics, immunology. In the best case, the sensitivity of these techniques did not make it possible to detect less than one residual cell in 100, a very insufficient sensitivity threshold to help clinician to decide for adequate treatment and to evaluate the quality control of the graft. The treatments envisaged must be carried out in order to obtain hematological remission and if possible a complete eradication of the Ph1 (+) cells (cytogenetic remission) with regard to chronic myeloid leukemia, the evolution takes place in two stages: A first chronic or myelocytic phase easily controlled by usual therapies then a second inconstant transition phase called acceleration with resistance to conventional chemotherapy, following which an acute transformation occurs, often of the terminal acute myelogenous leukemia type, constantly fatal, inevitable on average 3 to 4 years after diagnosis.

### **6. Contribution of oncocytogenetics in chronic myeloid leukemia**

The molecular consequence is the formation of a *BCR-ABL* fusion gene, transcribed into 8.5 Kb mRNA and translated into 210 Kd protein with greater tyrosine kinase activity compared to the normal protein of the proto oncogene c-*ABL* from 145 Kb, this protein is involved in the pathological process of CML [15]. The molecular biology techniques applied to DNA, mRNA (RT-PCR) and encoded


**Table 2.**

*The chromosomes involved and their molecular consequences.*

**Figure 5.**

*Schema the Philadelphia chromosome t(9;22)(q34;q11) results in the fusion of* BCR *genes on chromosome 22 and* ABL *on chromosome 22. The fusion protein has a strong activity tyrosine kinase responsible for tumor development.*

proteins have made it possible to specify the nature of the molecular events resulting from the rearrangement of *BCR-ABL* (**Table 2**)**.**

Fluorescent in situ hybridization (FISH) using specific probes provides a useful tool for the detection of t(9;22)(q34;q11) and *BCR-ABL* rearrangement [16] (**Figure 3**). The fusion protein has a strong activity tyrosine kinase responsible for tumor development (**Figure 5**)**.**
