Acute Lymphoblastic Leukemia, Classification, Clinical features and Diagnosis

Background: Leukemias are classified as lymphoid or myeloid, dependent on the type of stem cell that is affected. In addition, leukemia is classified as chronic or acute. Acute leukemia is a production of bone marrow-derived immature cells (blasts), include solid organs or peripheral blood. The FAB Cooperative Group original classification scheme proposed to divide1 ALL into three subtypes (L1 - L3). Currently, the world health organization (WHO), modify FAB classification depending on immunophenotype. Symptoms presence of anemia, splenomegaly, and thrombocytopenia, and those are naturally present at diagnosis, indicating the degree to which leukemic lymphoblasts have replaced the bone marrow and the first mark to an ALL diagnosis is typically an abnormal complete blood count result. Objective: To introduce causes of acute lymphocytic leukemia, recent classification methods, diagnosis, and symptoms and diagnosis. Conclusion: Acute lymphocytic leukemia occurs due to a defect in the bone marrow and is classified into several types. The most important classification by the World Health Organization is depending on immunophenotype. The main symptoms are the increase in white blood cells with anemia and thrombocytopenia. Keywords: Acute Lymphoblastic Leukemia, Blood


Introduction
Abnormal production of blood cells in the bone marrow and blood-forming organs leads to a malignant disease usually referred to as leukemia, which can be categorized according to the rate progression [1]. Leukemia etiology is poorly described, with most authors finding it to be multifactorial. Thus, viral infections (Epstein Barr), ionizing radiation exposure, chromosomal abnormalities (Down syndrome), chemical compounds (benzene), or families with leukemic history/ members constitute the risk factors [2].

Classification
Leukemia is a class of malignant hematologic disorder with mesenchymal Vol.19.Issue 2,December 2020 Acute Lymphoblastic Leukemia, Classification, Clinical features and Diagnosis Fatimah Kadhim Ibrahim AL-Mahdawi (lymphoid or myeloid) origin arising from the bone marrow, produces a high number of abnormal hematopoietic cells in terms of their proliferation, differentiation, and cell death programming (apoptosis) [3]. Leukemias are classified as lymphoid or myeloid, dependent on the type of stem cell that is affected. In addition, leukemia is classified as chronic or acute [4].

Acute Leukemia
Acute leukemia is a production of bone marrow-derived immature cells (blasts), include solid organs or peripheral blood. Lymphoid leukemia is derived from the lymphoid stem cells, which normally give rise to the lymphocytes (T-cells, B-cells, dendric cells, natural killer cells, and plasma cells) [5]. For several forms of leukemia, the ratio of blast cells essential for acute leukemia diagnosis is greater than twenty percent, and don't need any minimum percentage of blast cell when certain morphological and cytogenetic characteristics are present [6].

Types of Acute Leukemia
Acute leukemia is divided into two main types acute lymphoblastic leukemia and acute myeloid leukemia dependent on the origin of whether the blasts are present to be lymphoblasts or myeloblasts [7].

Acute Lymphoblastic Leukemia (ALL)
Acute lymphoblastic leukemia. "Acute" means leukemia will develop rapidly and will be lethal within a few months if untreated. "Lymphoblastic" means that it develops from early immature forms of lymphocytes, a type of leukocytes [8].

Classification of ALL
The classification of ALL by French-American-British is based on morphology and cytochemical staining of blasts [9] Figure (1). The FAB Cooperative Group original classification scheme proposed to divide1 ALL into three subtypes (L1 -L3) [10]. Table 1 explains the characteristics of three subgroups of ALL as reported by Conter et al., 2004 [11]. Recent years have seen tremendous progress in uncovering genetic lesions that influence the biology of ALL. In recognition of these advances, 2008 WHO classification incorporated the category of B-lymphoblastic leukemia/lymphoma with recurrent genetic abnormalities into the classification of precursor lymphoid neoplasms. Based on the knowledge available at the time, genetic lesions associated with distinct clinical features, immunophenotype, prognosis, or other unique biological characteristics were included in this category [14].
Immunophenotyping is an important adjunct to diagnosis and is helpful in confirming the diagnosis as well as lineage allocation to leukemia. When interpreting the immunophenotype data, one should keep in mind that no single antigen is specific for any neoplasm and that combining morphologic features and a panel of antigenic markers is necessary to obtain a correct diagnosis In addition, the combinations of markers expressed are to some extent reflective of the normal B-and T-cell development and can be used to determine the stage of development at which the leukemia transformation happened Table (2). In B-ALL this stage of maturation frequently correlates with the underlying cytogenetic abnormality. In T-ALL, the stage of maturation has been shown to correlate with survival in some studies. Finally, it must be pointed out that the expression of myeloid antigens is seen frequently in B-and T-ALL and does not preclude the diagnosis of ALL. Similarly, Blineage antigens can be expressed in T-ALL and vice versa. The criteria for making the diagnosis of acute leukemias of ambiguous lineage have been extensively revised in the 2008 World Health Organization (WHO) classification. The requirements for assigning more than 1 lineage to given leukemia are summarized in Table (3).

Clinical features of ALL
Symptoms and signs of acute leukemia are caused by blasts cells infiltrating the bone marrow or extramedullary [10]. The signs are anemia, splenomegaly, and thrombocytopenia [1]. Others common symptoms and signs include fever, fatigue, weight loss, loss of appetite, malaise, palpitations, shortness of breath, dizziness, cold sensitivity, paleness, bleeding and easy bruising, sore throat, problems in vision, pain in joints, nausea, night sweats, heaabdominal abdominal discomfort, Feeling of fullness in the abdomen [15].

Diagnosis of ALL
Abnormal leukocyte, thrombocytopenia and anemia are naturally present at diagnosis, indicating the degree to which leukemic lymphoblasts have replaced the bone marrow [16]. The first mark to an ALL diagnosis is typically an abnormal complete blood count result. A raised leukocyte (WBC count more than 10.000/mm3) [12]. Peripheral blood smears show blasts cells. Present thrombocytopenia (platelet count less than 100.000/mm3), and also anemia is present (hemoglobin less than 10g/dL), which is typically normocytic and normochromic with decrease reticulocytes number[17].

Conclusions
Acute lymphocytic leukemia occurs due to a defect in the bone marrow and is classified into several types. The most important classification by the World Health