**Table 1.**

**119**

**Figure 3.**

**Figure 1.**

**Figure 2.**

*patient with different treatment options.*

*The National Comprehensive Cancer Network (NCCN) guidelines stratify patients on low and high risk* 

*Cytogenetic and Genetic Advances in Myelodysplasia Syndromes*

*DOI: http://dx.doi.org/10.5772/intechopen.97112*

*International Prognostic Scoring System (IPSS).*

*Revised International Prognostic Scoring System (IPSS-R).*

*The World Health Organization (WHO) classification of Tumours of Haematopoetic and Lymphoid Tissues defines MDS.*

#### *Cytogenetic and Genetic Advances in Myelodysplasia Syndromes DOI: http://dx.doi.org/10.5772/intechopen.97112*


#### **Figure 1.**

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

**118**

**Name** **MDS, unclassifiable (MDS-U)**

with 1% blood blasts

with single lineage dysplasia and pancytopenia

based on defining cytogenetic abnormality

Refractory cytopenia of childhood

*PB monocytes must be <1 × 109/L.*

*†If SF3B1 mutation is present.*

**Table 1.**

*The World Health Organization (WHO) classification of Tumours of Haematopoetic and Lymphoid Tissues defines MDS.*

*‡One percent PB blasts must be recorded on at least 2 separate occasions.*

1–3

1–3 *\*Cytopenias defined as: hemoglobin, <10 g/dL; platelet count, <100 × 109/L; and absolute neutrophil count, <1.8 × 109/L. Rarely, MDS may present with mild anemia or thrombocytopenia above these levels.* 

None

BM <5%, PB

Any

<2%

0

1–3

<15%

BM <5%, PB

MDS-defining abnormality

<1%, no Auer

rods

1

3

None or any

BM <5%, PB

Any

<1%, no Auer

rods

1–3

1–3

None or any

BM <5%,

Any

PB – 1%,‡ no

Auer rods

**Dysplastic** 

**Cytopenias\***

**Ring** 

**BM and PB** 

**Cytogenetics by conventional karyotype analysis**

**blasts**

**sideroblasts as** 

**% of marrow** 

**erythroid** 

**elements**

**lineages**

#### *International Prognostic Scoring System (IPSS).*


#### **Figure 2.**

*Revised International Prognostic Scoring System (IPSS-R).*

#### **Figure 3.**

*The National Comprehensive Cancer Network (NCCN) guidelines stratify patients on low and high risk patient with different treatment options.*

implications of specific cytogenetic abnormalities on the Revised International Prognostic Scoring System (IPSS-R). In addition, the genetic profile of a patient's disease may dictate which therapy is most appropriate (**Figure 2**).

In fact, risk stratification in the first step in the care of newly diagnosed MDS is crucial, it help to convey disease severity, can set expectations (overall survivor for months, years, or decade) and is important to define treatment strategy.

The National Comprehensive Cancer Network (NCCN) guidelines stratify patients on low and high risk patient with different treatment options (**Figure 3**).

#### **5. Cytogenetics**

Conventional prognostic scoring of MDS is based on the extent of cytopenia, the percentage of bone marrow blast infiltration, and karyotype abnormalities [8, 9].

Metaphase cytogenetic show presence of abnormalities in approximately 50% of MDS. Some of cytogenetic abnormalities are characteristic of MDS, they may be considered as specific to MDS if the clinical context is appropriate.

Only del(5q) may be considered as MDS subtype. Therefore, the 2016 revision of the WHO classification considered cases with del(5q) plus one other abnormality to be categorized as MDS with isolated del(5q), providing the second abnormality is not del(7q).

Acute myeloid leukemia (AML) is characterised by balanced abnormalities wich predominate, in contrast of MDS where unbalanced abnormalities are more common. Overall, the most frequent abnormalities are loss of the Y chromosome (-Y), del(5q), +8, del(20q), and − 7 [10, 11].

On the other hand, cytogenetic abnormalities are more frequent in therapyrelated MDS (t-MDS) than de novo MDS, being reported in 70–90% cases [12].

Thus, a constitutional karyotype on a blood sample cultivated using phytohemaglutin like a mitogen can be realised in these two cases for a right interpretation of the cytogenetic response after treatment.

#### **5.1 The deletion of 5q and "5q- syndrome"**

The interstitial deletion of the long arm of chromosome 5 (del (5q)), can be considered the most frequent cytogenetic aberration in MDS, it occurs in 15% of patients with MDS. The "5q syndrome" is defined by an isolated del (5q) and an absence of excess blast, on the peripheral blood or the marrow. The IPSS includes a patient with del (5q) isolated in a favorable group. These patients have distinct morphological characteristics, thrombocytosis is found in one third of patients, macrocytic anemia and hypolobulated megakaryocytes, on the other hand, showed little dysplasia along the granulomonocytic and erythroid lines. The erythroid lineage can be hypoplastic.

The prognosis is favorable, overall survival for patients with 5q- is prolonged and the risk of progression to AML is lower than other patients with MDS. Even without treatment, clonal evolution is rarely reported. The prognosis is indeed dominated by the consequences of chronic transfusions, but these patients respond dramatically to the immunomodulating agent lenalidomide [13].

The 5q suppression can vary in size, but invariably affects bands q31 to q33. A common 5q33 deletion spanning more than 1.5 Mb and encompassing 42 genes has been reported. A model of haploinsufficiency in which the loss of a single copy of one or more genes possibly responsible for the 5q syndrome is suggested, and this may be explained by the absence of recurrent point mutation or cryptic deletion on the allele 5q normal.

**121**

*Cytogenetic and Genetic Advances in Myelodysplasia Syndromes*

often subclonal, fluctuating independently of blast counts.

Prognostic value on overall survival and risk of transformation.

Trisomy 8 + 8, (10–15%) that sometimes results from germinal mosaicism, is

Chromosome 7 anomalies comports del(7q), monsomy 7 (−7/del(7q)), or more rarely t(1;7), are second in frequencies after del(5q) (10%) and they have a poor

Prognostic values can be possibly distinct according to regions of deletion. In fact, many and different minimal regions of deletion have been noted in 7q35–36. Monosomy 7 can change constitutional bone marrow failures syndromes (FA, Down syndrome) or AA, or arise after radiation or toxic exposure. It is the most frequent alteration in childhood MDS where it is often associated with a degree of

Now it s known that G-CSF treatment may select a − 7 clone, and that 7q is a

Patients with −7/del(7q) are characterized by neutrophil functional impairment, they are exposed to severe infections. Those patient is very have poor response to intensive chemotherapy but respond better to hypomethylating agents [14, 15].

The IPSS-R considers the 3q26 alterations: inv.(3)(q21q26), and t(3;3)(q21;q26) as pejorative abnormalities, they rearrange the MECOM (MDS1/EVI1) locus with complex oncogenic roles and may be accompanied by thrombocytosis. Numerous other partners of EVI1 are reported as PRDM16 in t(1;3)(p36;q21) and RUNX1 in

Abnormalities of chromosome 17 are multiple, it can be deletion, monosomy, unbalanced translocation or isochromosome 17 which involve the loss of one TP53 locus, they are described in sMDS/AML after treatment with chemotherapy and/or radiotherapy, usually its associate with other complex genetic abnormalities.

It has been proved that chromosome 17p deletion with consistent involvement of TP53 gene located at 17p13 is associated with vacuolated pseudo-Pelger-Huet granulocytes. Those patients have poor prognosis both in MDS and AML.

Karyotypes is considered as Complex (15%) by the presence of at least 3 anomalies that are thought to result from alterations in DNA repair or checkpoint signalling. Complex karyotypes are usully heterogeneous. The prognosis of patient having complex karyotype is worsening with each additional aberration, rather than by the chromosomes involved (most frequently, 5, 7 and 17). Complex karyotypes are by essence chemoresistant, but interesting results with the hypomethylating agent

According to the IPSS, other abnormalities can be considered as favourable:

*DOI: http://dx.doi.org/10.5772/intechopen.97112*

**5.3 Monosomy 7/deletion 7q**

myeloproliferation.

genetically instable region.

**5.4 3q26 abnormalities**

t(3;21)(q26;q22).

**5.5 17p-/-17 and TP53 mutations**

**5.6 Complex karyotypes**

**5.7 Others abnormalities**

decitabine have been described by some studies.

**5.2 Trisomy 8**
