5. Oncofusion proteins related with AML

2.3. RAS mutations

150 Myeloid Leukemia

AML patients, respectively [12].

4. Molecule analysis of mutations in AML

Favorable inv (16) or t(16;16)

Intermediate Normal cytogenetics

t(8;21) t(15;17)

Isolated +8 t(9;11)

Poor Complex (≥3 clonal abnormalities)

inv (3) or t(3;3) t(6;9) t(9;22)

Table 2. Genetic risk classification of acute myeloid leukemia.

Monosomal karyotype 5/5q or 7/7q

Risk Cytogenetics Molecular

Other non-good and non-poor changes

11q23 rearrangements other than t(9;11)

3. Class II mutations

(OS) [12, 13].

Mutations in N-RAS and K-RAS occur in AML as well as solid Tumors in about 10 and 5% of

In addition to class I mutations, in AML patients, mutations in brain and acute leukemia gene (BAAL), MLL-MLLT3 gene fusion created by the t(9;11)(p22;q23) translocation is associated with intermediate prognosis in AML, nucleoplasmin 1(NPM1), CCAAT/enhancer-binding protein α (CEBPα), and Wilms tumor gene (WT-1) have also been detected. Lately, mutations in DNMT3A, encode DNA methyltransferases that catalyze the addition of a methyl group to the cytosine residue of CpG dinucleotides, have been recognized in one-third of de novo AML patients with intermediate-risk cytogenetics. Genomes with DNMT3A mutations commonly harbored extra mutations in NPM1, IDH1, and FLT3. The incidence of any DNMT3A mutation, alone or in combination with FLT3 ITD mutation, is related with lower overall survival

The single most important prognostic factor in AML is cytogenetic testing of bone marrow samples. Results are highly predictive of response to induction chemotherapy, relapse risk, and overall survival (OS). Approximately 50–60% of newly diagnosed AML patients can be detected by cytogenetic abnormalities [14]. To recognize cytogenetic abnormalities,

> Normal cytogenetics with: Isolated biallelic CEBPA mutation NPM1 mutation without FLT3 ITD

inv (16) or t(16;16)

t(8;21)

KIT mutation in core binding factor leukemia:

Normal cytogenetics with: FLT3 ITD

In total, 749 chromosomal aberrations have been recorded in AML [19]. Table 3 shows the common chromosomal aberrations and their corresponding Oncofusion Proteins in AML [12].

In conclusion, AML is a highly aggressive heterogeneous malignant disease, classified by genetic abnormalities that define subgroups of distinct biological and clinical features. Despite best efforts at targeted therapy, therapeutic approaches have stuck to "one-size fits all" conventional chemotherapy because of lack of targeted therapeutic options.


Table 3. Acute myeloid leukemia (AML)-associated Oncofusion proteins.
