Evaluating the clinical significance of mutation status in Syrian newly diagnosed acute myeloid leukemia patients with normal karyotype.

The FMS-like tyrosine kinase-3 internal tandem duplication (-ITD) is one of the most prevalent mutations, affecting between 20 and 30 percent of cases in patients with acute myeloid leukemia (AML). The Patients with a -ITD mutation have a poor prognosis. In the present study, we investigated the (ITD-TKD) mutations in 100 newly adult Syrian patients with AML-Normal karyotype (NK).

Prognostic Relevance of DNMT3A, FLT3 and NPM1 Mutations in Syrian Acute Myeloid Leukemia Patients.

Objective: Among all types of hematological neoplasms, acute myeloid leukemia (AML) has the highest death rate. Recently, cytogenetic and molecular genetics are crucial in the management, as a consequence of their effect on AML pathogenesis, classification, risk-stratification, prognosis and treatment.

Methods: 100 Syrian adults with Normal Karyotype (NK) newly diagnosed  AML patients were included in this study, all cases confirmed histologically and immunohistochemically.

Acute myeloid leukemia due to germline CEBPA mutation in a Syrian family.

Background: Familial cases of adult acute myeloid leukemia (AML) with germline-mutated CCAAT/enhancer-binding protein-α (CEBPA) gene are a rare entity classified in World Health Organization (WHO) classification 2016. Most families reported in the literature show an autosomal dominant inheritance pattern consistent with a single-gene mutation.

Methods: Here we studied a Syrian family with four individuals suffering from AML for CEBPA gene mutations by Sanger sequencing.

Frequency of FLT3 Internal Tandem Duplications in Adult Syrian Patients with Acute Myeloid Leukemia and Normal Karyotype.

Objective: Activating mutations of the fms-like tyrosine kinase 3 gene (FLT3) by internal tandem duplications (ITDs) in the juxtamembrane domain (JMD) have been reported in ~30% of adult acute myeloid leukemia (AML) patients with cytogenetically normal karyotype (CN). However, FLT3/ITD mutations are frequently accompanied with leukocytosis, high percentage of blasts in bone marrow (BM), and increased the risk of treatment failure in AML patients. FLT3-ITD mutated AML patients mainly with normal karyotype have higher relapse probability and shorter duration of complete remission (CR) after chemotherapy, so FLT3-ITD mutation is considered as an independent poor prognostic factor in AML.

De novo adult acute myeloid leukemia with two new mutations in juxtatransmembrane domain of the FLT3 gene: a case report.

Background: Approximately 30% of adult acute myeloid leukemia (AML) acquire within fms-like tyrosine kinase 3 gene (FLT3) internal tandem duplications (FLT3/ITDs) in their juxtamembrane domain (JMD). FLT3/ITDs range in size from three to hundreds of nucleotides, and confer an adverse prognosis. Studies on a possible relationship between of FLT3/ITDs length and clinical outcomes in those AML patients were inconclusive, yet.

A new childhood ALL case with an extremely complex karyotype and acute spontaneous tumor lysis syndrome.

Background: B cell precursor acute lymphoblastic leukemia (B-ALL) is the most common malignancy of childhood, with, after corresponding treatment, an overall complete remission rate of 90%. Approximately 75% of B-ALL cases harbor recurrent abnormalities, including so-called complex karyotypes (CK). Tumor lysis syndrome (TLS) is a metabolic abnormality which may arise during cancer therapy and also, extremely rarely, as spontaneous TLS before initiation of chemotherapy in patients with ALL.

An acquired stable variant of a dicentric dic(9;20) and complex karyotype in a Syrian childhood B-acute lymphoblastic leukemia case.

Background: About 25 years ago, the acquired chromosome abnormality dicentric dic(9;20)(p11 ~ 13;q11) was seen described as a non-random aberration in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Yet, about 200 cases were reported. However, dicentric dic(9;20) is a subtle abnormality which easily may be mixed up with monosomy 20 and/or del(9p).

De novo Balanced Robertsonian Translocation rob(22;22)(q10;q10) in a Woman with Recurrent Pregnancy Loss: A Rare Case.

Background: Recurrent pregnancy loss (RPL), one of the most common complications of pregnancy, is responsible for significant emotional distress to the couple desiring to conceive. In almost 50% of the cases, the etiology remains unknown. The frequency of chromosomal structural rearrangements associated with a history of RPL in couples varies between 2% to 8%.

Geographical distribution of β-globin gene mutations in Syria.

Objectives: β-Thalassemia disease is caused by mutations in the β-globin gene. This is considered as one of the common genetic disorders in Syria. The aim of this study was to identify the geographical distribution of the β-thalassemia mutations in Syria.

Association of Methylenetetrahydrofolate Reductase C677T and A1298C Gene Polymorphisms With Recurrent Pregnancy Loss in Syrian Women.

C677T polymorphism of the methylenetetrahydrofolate reductase ( MTHFR) gene was a risk factor for recurrent pregnancy loss (RPL), but few studies have confirmed a possible role of MTHFR A1298C polymorphism in RPL risk. This study was carried out to determine the influence of the MTHFR gene polymorphisms in RPL Syrian women. A case-control study was performed on 2 groups (106 healthy and 100 RPL women).

Childhood pre-B cell acute lymphoblastic leukemia with translocation t(1;19)(q21.1;p13.3) and two additional chromosomal aberrations involving chromosomes 1, 6, and 13: a case report.

Background: The translocation t(1;19)(q23;p13), which results in the TCF3-PBX1 chimeric gene, is one of the most frequent rearrangements observed in B cell acute lymphoblastic leukemia. It appears in both adult and pediatric patients with B cell acute lymphoblastic leukemia at an overall frequency of 3 to 5%. Most cases of pre-B cell acute lymphoblastic leukemia carrying the translocation t(1;19) have a typical immunophenotype with homogeneous expression of CD19, CD10, CD9, complete absence of CD34, and at least diminished CD20.

First report of prevalence c.IVS1+1G>A and del (GJB6-13S1854) mutations in Syrian families with non-syndromic sensorineural hearing loss.

Objective: Mutations in GJB2 and GJB6 genes are a frequent cause of congenital non-syndromic hearing loss (NSHL). Mutational screening has usually focused on coding region of GJB2 gene. A few studies have been conducted on the non-coding region and exon 1.

Acute promyelocytic leukemia with the translocation t(15;17)(q22;q21) associated with t(1;2)(q42~43;q11.2~12): a case report.

Background: Acute promyelocytic leukemia is characterized by a typical reciprocal translocation t(15;17)(q22;q21). Additional chromosomal abnormalities are reported in only 23-43 % of cases of acute promyelocytic leukemia.

Case Presentation: Here we report the case of a 46-year-old Syrian Alawis woman with acute promyelocytic leukemia with the typical t(15;17) translocation, but with a second clone presenting a t(1;2)(q42~43;q11.

Correlation of p210 BCR-ABL transcript variants with clinical, parameters and disease outcome in 45 chronic myeloid leukemia patients.

Purpose: The aim of this study was to search the BCR/ABL 1 fusion gene in 45 chronic myeloid leukemia (CML) Syrian patients using nested reverse transcription polymerase chain reaction (RT-PCR) and compare our results with those of conventional cytogenetics and molecular cytogenetics methods.

Methods: 45 bone marrow or peripheral blood samples from untreated CML patients in chronic phase (CP) were obtained at diagnosis, and analyzed by nested RT-PCR, conventional cytogenetics and molecular cyto-genetics methods.

Results: 45 patients examined were positive for some type of BCR/ABL1 fusion gene rearrangement.

Masked inv dup(22)(q11.23), tetrasomy 8 and trisomy 19 in a blast crisis-chronic myeloid leukemia after interrupted Imatinib-treatment.

Background: The Philadelphia (Ph) chromosome, or derivative chromosome 22 [der(22)], is a product of the reciprocal translocation t(9;22). It is the hallmark of chronic myelogenous leukemia (CML). It results in juxtaposition of the 5' part of the BCR gene on chromosome 22 to the 3' part of the ABL1 gene on chromosome 9.

Deletion 9p23 to 9p11.1 as sole additional abnormality in a Philadelphia positive chronic myeloid leukemia in blast crisis: a rare event.

Background: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of a derivative chromosome 22 [der(22)] commonly called Philadelphia chromosome (Ph). The Ph chromosome is a product of the reciprocal translocation t(9;22)(q34.1;q11.

Chromosomal aberration leads to recurrent pregnancy loss and partial trisomy of 5p12-15.3 in the offspring: report of a Syrian couple and review of the literature .

Here we describe a Syrian couple having recurrent pregnancy loss in the first trimester, fetal malformations, and/or neonatal death. The father had a balanced chromosomal translocation t(5;15), an sY125 microdeletion of locus b in the azoospermia factor (AZF) gene, and an MTHFR C677T homozygous polymorphism with normal phenotype. Interestingly, his healthy wife had another MTHFR A1298C homozygous polymorphism.

Hyperdiploidy associated with T315I mutation in BCR-ABL kinase domain in an accelerated phase-chronic myeloid leukemia case.

Background: Chronic myeloid leukemia (CML) is genetically characterized by the occurrence of a reciprocal translocation t(9;22)(q34;q11), resulting in a BCR/ABL gene fusion on the derivative chromosome 22, i.e. the Philadelphia (Ph) chromosome.

Prenatal molecular diagnosis of β-thalassemia and sickle cell anemia in the Syrian population.

Our objective was to evaluate the prenatal diagnosis (PND) of β-thalassemia (β-thal) and sickle cell anemia in Syria. Mutations detected from blood of at-risk couples and 55 amniotic fluid samples collected at the second trimester of pregnancy (14-22 weeks' gestation) were characterized. Molecular screening and direct DNA sequencing of the HBB gene was carried out.

An adult B-cell precursor acute lymphoblastic leukemia with multiple secondary cytogenetic aberrations.

Background: We report a clinically diagnosed acute lymphoblastic leukemia (ALL) with yet unreported secondary chromosomal aberrations.

Results: A complete cytogenetic and molecular cytogenetic analysis, using GTG banding, fluorescence in situ hybridization (FISH) and array-proven multicolor banding (aMCB), for a female patient with clinically diagnosed ALL and immunophenotypically confirmed pre-B ALL (FAB classifications), revealed the presence of a complex structural rearrangement, der (2) (20qter- > 20q13.33::2q21- > 2p14::2q21 > 2qter) along with t (9;22) (q34;q11), t (12;14) (q12;p12) and a monosomy of chromosome 7.

Molecular update of β-thalassemia mutations in the Syrian population: identification of rare β-thalassemia mutations.

β-Thalassemia (β-thal) is an autosomal recessive disorder characterized by variable degrees of anemia, bone marrow hyperplasia, splenomegaly, and complications related to the severity of the anemic state. The β-thalassemias result from mutations in and around the β-globin gene (HBB) located as a cluster on the short arm of chromosome 11. In Syria, β-thal is highly prevalent.