Leukemia, Acute Myeloid

Alternative Names

  • AML
  • Leukemia, Acute Myelogenous
  • Acute Myeloblastic Leukemia
  • Acute Granulocytic Leukemia
  • Acute Nonlymphocytic Leukemia
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WHO-ICD-10 version:2010

Neoplasms

Malignant neoplasms

OMIM Number

601626

Mode of Inheritance

Autosomal dominant

Gene Map Locus

3q24, 3q25.1, 3q28,4q11-q12, 4q12,5q35,8p12,9p24, 9q34.1,10p12,11q14, 11q23.3,12p13,13q12,16q22,19p13.3, 19q13.1,21q22.3

Description

Acute Myeloid or Myelogenous Leukemia (AML) is a form of leukemia characterized by the rapid development of immature, abnormal white blood cells, known as myeloblasts. The myeloblasts are unable to take up the functions of healthy blood cells and tend to accumulate in the bone marrow and blood, crowding out the normal healthy cells. Although AML starts within the bone marrow, it quickly moves through the blood to the lymph nodes, liver, spleen, CNS, and the testes. According to the FAB classification, there are eight sub-types of AML, based on which of the blood cells are abnormal. Symptoms of AML include fever, fatigue, shortness of breath, loss of appetite and weight, easy bruising and bleeding, and increased risk of infection. Since this form of leukemia is acute, the disease develops very rapidly, and can be fatal if not treated within weeks.

AML usually affects people over the age of 40, and is more commonly seen in men than in women. It is estimated that 1 in 272 individuals will be diagnosed with AML during their lifetime. Diagnosis of AML depends upon physical examination, blood profile on the basis of Complete Blood Count (CBC), blood chemistry studies, peripheral blood smear, as well as bone marrow aspiration, and cytogenetic analysis. Chemotherapy is the primary mode of treatment, and involves an induction phase, in which leukemic cells are brought down to the lowest level possible, followed by a consolidation phase, in which any residual disease is also eliminated.

Molecular Genetics

AML has been seen to arise, both due to germ-line as well as somatic mutations. The familial form of the disease is transmitted in an autosomal dominant manner. In either case, over 50% of the abnormality involves a gross chromosomal defect, which could be one of the following: t(15;17)(q21;q11), t(11;17)(q23;q11), t(11;17)(q13;q11), t(5:17)(q31;q11), or t(17;17). Some of these chromosomal translocations are associated with specific subtypes of AML. For instance the t(15;17) is associated with Acute Promyelocytic Leukemia.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
208900.1LebanonMale Ataxia; Muscular hypotonia; Polyneurop... NM_000051.3:c.7630-2A>C, NM_004972.3:c.1597A>THeterozygousAutosomalNair et al. 2018
208900.G.1Lebanon Acute myeloid leukemia... NM_004119.2:c.2504A>TSalem et al. 2017 two patients exhibit...

Other Reports

Kuwait

Al-Bahar et al. (1993) reported a Kuwaiti patient with a de novo acute myeloblastic leukemia associated with trisomy 4. Upon complete remission of the cancer, the karyotypic abnormality was found to disappear. One year later, Al-Bahar et al. (1994) studied the occurrence of leukemia subtypes in Kuwait between 1979 and 1989. AML occurred in 32.4% of a total of 723 cases. This incidence showed a progressive increase with increase in age. In 2004, Al Bahar et al. undertook cytogenetic analysis of 45 patients, 10 of them children, with de novo AML. Clonal chromosomal abnormalities were detected in 35 patients; the most common aberrations being t (15;17) (q22;q11), t (8;21) (q22;q22), inv (16) (p13q22), trisomy 8, monosomy 7, and del (5q). In addition, 11 patients revealed miscellaneous chromosomal abnormalities not previously described. Patients with AML-M3 showed the highest frequency of chromosomal changes.

Lebanon

El Hajj et al. 2015 studied the effects of retinoic acid (RA) and arsenic trioxide (arsenic) on acute myeloid leukemia (AML) cell lines with mutated NPM1, primary AML cells collected from three patients, and elderly AML patients with normal karyotype and mutated NPM1. Exposure to RA and arsenic was noted to induce selective apoptosis and upregulation of p53 in AML cell lines and primary samples with mutant NPM1. Combined RA/arsenic treatment also restored the nuclear localisation of NPM1 and promyelocytic leukemia (PML) nuclear bodies (ex vivo and in vivo), and reduced bone marrow blasts in three patients. El Hajj et al. suggested their findings support the addition of RA to chemotherapy in NPM1 mutant AMLs.

To understand the molecular response of predictive markers to treatment, Salem et al. 2017 studied 12 adult patients with acute myeloid leukemia (AML) who were positive for both NPM1 and FLT3 mutations at the time of diagnosis. Molecular testing on bone marrow samples were carried out: at diagnosis; within regular intervals before and during chemotherapy and allo-SCT (allogeneic stem cell transplantation); and every three months after allo-SCT. All patients were positive for NPM1 frameshift mutations at diagnosis. Ten of them had FLT3 internal tandem duplications, whereas two patients were positive for FLT3 D835V mutation. All patients had tested negative for FLT3 mutation after induction and apart from two patients who had early deaths, the others remained negative. Only two out of 10 patients became negative for NPM1 mutations after induction and eight additional patients tested negative for NPM1 mutations after allo-SCT. Salem et al. noted that patients with a < 4-log reduction in peripheral blood minimal residual disease (PB-MRD) had better disease free survival and overall survival, supporting the prognostic significance of early NPM1 mutation PB-MRD.

Oman

Ghosh et al. (2000a, 2000b) reported an 18-year old female, who was diagnosed with acute myelomonocytic leukemia. The diagnosis of acute myelomonocytic leukemia was confirmed by bone marrow aspirate examination, which showed 18-25% blast cells, 5-10% of which contained pseudo-Chediak Higashi granules. The immunophenotype was positive CD 7, CD13, CD 33, CD45 and negative Tdt, Ia and P glycoprotein. The patient had normal 46 XX karyotype on G-banded karyotyping from bone marrow aspirate. The patient was started on combination chemotherapy with Daunorubicin and cytosine arabinoside. Chemotherapy was followed by complications of monocytosis, retinopathy, and choroidal infiltration. After two weeks, her visual acuity improved and she had complete improvement of her vision with no evidence of any deposits and normalization of the peripheral blood picture without any therapeutic intervention, and was in marrow remission.

Knox-Macaulay et al. (2002) reported pseudotumor cerebri in a young Omani female diagnosed with acute promyelocytic leukemia before starting treatment for her malignancy. The 16-year old patient presented with low grade fever and recurrent episodes of bleeding gums, epistaxis, easy bruisability and fatiguability for three weeks. Bone marrow aspiration and biopsy confirmed the diagnosis of APL with the t(15;17) chromosome translocation being demonstrated in 100% of cultured marrow cells. Her coagulation profile was suggestive of an incipient coagulopathy. The diagnosis of pseudotumour cerebri was made on the basis of her symptoms, ophthalmic evaluation and normal CT scan and confirmed by CSF examination (elevated CSF opening pressure of 420 mmH2O with normal proteins and glucose concentration and no cells). Chemotherapy led to clinical improvement and the bone marrow became morphologically normal with only 4% cultured marrow cells showing t(15;17) translocation. The elimination of the PML-RAR-alpha oncogene was confirmed by molecular studies.

A rare case of cytokine-mediated toxicity of all-trans retinoic acid (ATRA) involving the muscles which responded to dexamethasone was reported by Kannan et al. (2005) in an 18-year old girl. The patient had earlier been diagnosed with acute promyelocytic leukemia and was started on ATRA and idarubicin. She presented with a painful swelling on the left thigh and fever which did not settle with antibiotics, and was found to have elevated C-reactive protein and negative blood cultures. Venous thrombosis was excluded by Ultrasound Doppler, but increased uptake in the left thigh was shown by a technetium-tagged leucoscan. MRI revealed marked edema of the skin, subcutaneous tissue and the adductor muscles and marked muscle necrosis was evident on a gadolinium-enhanced T1-weighted transverse image. According to the above findings, ATRA was discontinued as it is known to cause myositis, and dexamethasone was started which improved the swelling and fever within 24-hours. It was then tapered after resolution of the swelling and ATRA was recommenced with no further complications and a repeat nuclear scan revealed normal appearance.

Udayakumar et al. (2007) conducted the first systematic cytogenetic study of AML in an ethnic Omani population. A total of 63 Omani patients (41 males, 22 females), with de novo AML, 18 of them children, were studied. According to the FAB criteria, most patients fell into the M2 morphological subtype. This was in contrast to reports from neighboring countries, where the M4 and M3 subtypes were more common. Chromosomal abnormalities were noticed in 62% of the patients, the most common ones being balanced translocations, including t(8;21), and t(15;17), trisomy 18, and monosomy 7. Later, Udayakumar et al. (2009) described a unique case of a 24-year-old Omani female with acute myeloid leukemia (AML) involving both chromosomes 9 presenting with an acquired pericentric inversion of breakpoints at 9p13 and 9q12, respectively, and with aberrant CD7 and CD9 positivity. Additionally, one der(9) also showed short arm deletion at 9p21 to the centromeric region including the p16 gene. The constitutional karyotype was found to be normal. AML was diagnosed in the patient during her second pregnancy at 30 weeks gestation. Udayakumar et al. (2009) concluded that this is probably the first report describing an acquired inv(9) involving both chromosomes 9 in AML.

Saudi Arabia

Gari et al. (2008) carried out direct DNA sequencing analysis for 129 patients with acute myeloid leukemia (AML).  Internal tandem duplication (ITD) mutations were identified in the FLT3 gene in 15 AML patients.  Also a G>C point mutation of exon 20 was identified in 11 AML patients.

Elyamany et al. (2014) did a molecular study in 97 Saudi patients with AML and found 18 cases positive for FLT3 mutations.

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