**2. Acute leukemia**

#### **2.1 Acute lymphoblastic leukemia**

ALLs are neoplasms composed of immature B (pre-B), T (pre-T) or NK-cells that are referred as ("lymphoblasts"), of which the majority is pre-B ALL (85–90% in children vs. 75% in adults) [1]. It is the most common cancer in children and accounts for a quarter of all childhood malignancies. Although there are as many adults with ALL as there are children with the disease, the relative frequency in adults is much lower. Worldwide, the overall incidence is approximately 1–2 per 100.000 people, with a peak incidence occurring in childhood and a second peak above the age of 50 years [6].

#### *2.1.1 Cytogenetic abnormalities*

Chromosomal aberrations are the hallmark of ALL and are often used to categorize patients. In B-ALL, recurrent chromosomal abnormalities are found in 80% of the patients, including numerical and structural changes as translocations, deletions and inversions. There are substantial differences in the frequencies of occurring of cytogenetic abnormalities between children and adults [1, 7–10]. For instance, the translocation 9;22 [*BCR-ABL1*] is observed in 2–5% of the children compared to in 30% of the adults, whereas the translation 12;21 [*ETV6-RUNX1*] is observed in 25% of the pediatric patients versus 3% in adult population. The hyperdiploid (gain of chromosomes) karyotype is present in 30–40% of the children compared to 3% in adults. Finally, translocation 4;11 resulting in the MLL-AF4 fusion gene, is detected in 60–80% of the infants (younger than 1 year old), whereas it is seen in only 2% of the patients up to 15 years and rare in adults. Hypodiploidy (loss of chromosomes) occurs in 5–6% of the ALL patients, independent of age.

Chromosomal translations occur less frequently in T-ALL compared to B-ALL (approximately 50–60%) and unlike in B-ALL their prognostic impact is not well defined and they are not used for risk stratification [10]. They are involved in both

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*CEBPA* most studied.

*Proteoforms in Acute Leukemia: Evaluation of Age- and Disease-Specific Proteoform Patterns*

the T-cell receptor and the non-T-cell receptor loci on the chromosome or aberrant expression of the transcription factor oncogenes. There is less association with age [8].

Survival in children with ALL is much better compared to adults, with the exception of infant ALL. In 60–80% of the cases, infant ALL is characterized by translocations involving 11q23, affecting the KMT2A gene. Aberrant KMT2A in ALL is associated with a high rate of early treatment failure and a very poor outcome (long-term event-free survival of 28–45%), even when treated with more aggressive chemotherapy regimens [11, 12]. Historically, pediatric T-ALL was considered as high-risk disease. With the introduction of therapy intensification in T-cell ALL, this has changed to outcomes comparable to B-cell ALL, resulting in a five-year OS rate of more than 90% [13]. However, within certain high-risk subgroups (e.g. infants or children ≥10 years of age), 25–30% still experience relapse, which has a dismal outcome even with hematopoietic stem cell transplantation. Death resulting from treatment toxicity remains a challenge with an estimated

10-year cumulative incidence of treatment-related death of 2.9% [14].

the different underlying biology should not be underestimated [8].

100.000 people, and the incidence strongly increases with age.

*2.2.1 Cytogenetic and molecular abnormalities*

**2.2 Acute myeloid leukemia**

Survival for ALL in adults is around 45%, but patients above the age of 60 suffer from inferior outcomes with only 10–15% long-term survival [10]. This is, at least partially, due to higher risk of medical comorbidities, the inability to tolerate standard chemotherapy regimens, and age-related unfavorable intrinsic biology such as Philadelphia chromosome positive, hypodiploidy and complex karyotype. However, as even the adolescents and young adults who lack medical comorbidities do significantly worse compared to their younger counterparts, the contribution of

In general, patients with AML have similar signs and symptoms as patients with ALL which mainly includes symptoms related to (pan)cytopenia. AML is the most common acute leukemia in adults, whereas it is relatively rare in children (accounting for only 10% of the acute leukemia) [15]. Overall, AML occurs in 3–5 cases per

AML is a very heterogeneous disease and the identification of AML-associated chromosomal translocations and inversions have led to the current 2016 World Health Organization (WHO) classification system [16]. In this classification, eight recurrent genetic abnormalities (e.g. translocation (15;17) [*PML-RARA*], translocation (8;21) [*RUNX1-RUNX1T1*], inversion (16) or translocation (16;16) [*CBFB-MYH1*], translocation (9;11) [*MLLT3-KMT2A*], and translocation (9;22) [*BCR-ABL1*]) and their variants are included. In approximately 50 percent of patients, no cytogenetic abnormalities will be present, referred to as "normal karyotype" [17]. Additional classification in AML is provided by detection of one or more recurrent genetic mutations, with *NPM1*, *FLT3*, *IDH1*, *IDH2*, *RUNX1* and

Recently, the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) study has presented the molecular landscape of nearly 1000 pediatric AML patients that participated in several Children's Oncology Group (COG) clinical trials [18]. Like adult AML, they found that pediatric AML has one of the lowest rates of mutations as compared to other cancers as recognized by The

*DOI: http://dx.doi.org/10.5772/intechopen.90329*

*2.1.2 Prognosis*

the T-cell receptor and the non-T-cell receptor loci on the chromosome or aberrant expression of the transcription factor oncogenes. There is less association with age [8].
