Childhood Acute Lymphoblastic Leukemia: Molecular Correlates of Clinical
Outcomes: Comparison of Omani and American Children
Project Code:
Funds:
Funding Source:
Start Date:
Duration:
Team Members:
(SR/MED/CHLD/01/01)
270,000 OMR
His Majesty’s Trust Fund
02 May 2001
4 years
Researchers
Dr. Zakia Mohammad Al Lamki (P.I.)
Dr. Yasser Walli
Dr. Mathew Zachariah
Ms. Rayhanah Abdulmunim Al-Mjeni
Dr. Judith Margolin
Dr. Preethi Gunaran
Dr. Shah Wasifuddin
Dr. Wafa Bashir
Dr. Shanmugakonar Muralitharan
Ms. Khalsa Said Al-Kharusi
Dr. Marie-Claude Gingras
Dr. Richard Gibbs
Executive Summary
Objectives
This study was designed to examine the GEP differences between high-risk Omani and American
ALL patients with non-determined chromosomal translocations (NDCT) who were successfully
treated against those who relapsed.
Methods
Sophisticated and unique molecular techniques were employed. These included: Suppression
Subtraction Hybridization (SSH), cDNA Concatenated Sequencing (CCS) and Reverse
Transcriptase Real-time Quantitative Polymerase Chain Reaction (RT-RQ-PCR), which allows for
a broad assessment of gene expression. The patients were categorized as high-risk NDCT based
on one or several clinical features - high white blood cell count (WBC) at presentation, age - and
by the fact that they had none of the determinant chromosomal abnormalities detected by
conventional metaphase cytogenetics, modified cytogenetics techniques (interphase FISH),
and/or molecular (PCR) analytical methods.
Results
Since this type of molecular profiling can also be done by microarray, we also compared the
cDNA sequence with unknown function to sequences present on commercially available array
chips. Over 36% of the sequences we identified were not present on the most comprehensive
microarrays (Affimetrix human U133). Over 1,600 genes were identified. 110 genes were
analyzed by RT-RQ-PCR, 86 of which were previously known to be implicated in cancer. The
expression levels of three genes (GZMK, CASK, and CRSP2) were found to have potential
correlates with clinical outcomes. These genes exhibited significant fold expression in patients
with high risk ALL (NDCT) who did not relapse. The 3 identified genes were associated with
positive outcomes in the otherwise high risk (poor outcome) patients.
Conclusions
We were able to identify specific gene expression patterns that may help in the categorization of
pediatric ALL into risk groups. None of these genes has ever been previously reported in the
pathogenesis of ALL. Further work will be required to detect the role of these genes in the
prognosis of ALL in children. This research may produce a platform for understanding the
molecular aspects of ALL in relation to NDCT patients and the relapse status, since 40-60% of
such high-risk patients relapse and a significant proportion of clinically high-risk patients are
NDCT. This work represents the first time that Oman has contributed through international
collaboration to the world-wide effort to improve the diagnosis and treatment of pediatric ALL.
Besides the introduction of diagnostic tools and facilities, this project has nurtured the concept of
cutting edge science, facilitated knowledge sharing, and the transfer of technology and training.
Hypertension in Oman: Intervention Clinical Trial and Mapping of Genes
Project Code:
Funds:
Funding Source
Start Date:
Duration:
Team Members:
(SR/MED/PHYS/01/01)
278,000 OMR
His Majesty’s Trust Fund
02 May 2001
3 years
Researchers
Prof. Mohamed Hassan (P.I. )
Prof. Riad Bayoumi
Dr. Said Ali Al Yahyaee
Dr. Ali Jaffer Suleiman
Dr. Sulayma Amer Al-Barwani
Dr. Ali Talib Al Hinai
Mr. Saleh Al-Hadabi
Dr. Jawad Al Lawati
Dr. Deepali Jajui
Dr. Syed Rizwi
Support Staff
Mr. George Jessy
Mr. Ahmed Said Al Sawafi
Ms. Sawsan Al Sinani
Mr. Perez Ben
Research Assistants
Dr. Shanmugakonar Muralitharan
Ms. Hameeda Al Barwani
Mr. Mohammed Nasser Al Kindi
Mr. Nasarallah Mansoor Al-Toubi
Ms. Suleima Marhoon Al Zakwani
Ms. Bahiya Saif Al Toubi
Ms. Nasra Ali Al Bousaeedi
Ms. Salama Abdullah Al Hadedi
Ms. Gameela Mohamed Al Hadidi
Ms. Fawziya Mohamed Al Kindi
Ms. Ghasiya Sulaimn Al Amri
Ms. Zakiya Hamed Al Zakwani
Mr. AbdulHakeem Khalifa Al-Hinai
Mr. Suleiman Mohammed Al Riyami
Mr. Yagut Akbarova
Ms. Huda Talib Al Saadi
Mr. Abdullah Hamed Al Harasi
Dr. George Khaukha
Graduate Students
Ms. Sawsan Salim Al Sinani
Ms. Ghalia Mohamed Al Kasbi
Ms. Fatma Jaffar Al Lawati
Executive Summary
Objectives
To find the prevalence of hypertension and other emerging and known risk factors such as
diabetes mellitus and metabolic abnormalities in parents and their children in a homogeneous
Omani population; to identify genetic and environmental factors and the contribution of each to
the pathophysiology of hypertension and related diseases; to establish lifestyle and clinical
intervention programs for the prevention and treatment of hypertension and related metabolic
abnormalities.
Methods
A total of 1277 subjects, aged 16-80 years, from five large, extended and highly consanguineous
families from five villages around Nizwa (Dakhylia region) voluntarily consented to participate in
the study. Family trees were constructed from information collected from family elders and later
confirmed by DNA mapping Blood pressure was measured for 24 hours and other detailed
cardiovascular parameters were measured under resting and stressful laboratory conditions using
the latest non-invasive technologies. Blood samples were collected for biochemical parameters
and DNA extraction. Diabetes and hypertension were defined according to recent international
definitions.
Results
In the adult population, the prevalence of hypertension was 31%, diabetes 5.5 %. Impaired
glucose tolerance was 12%, high cholesterol 37%, high triglycerides 18%, overweight 13% and
the metabolic syndrome 22%. The prevalence of borderline hypertension in the young offspring of
one or two hypertensive parents was 31%. Heritability estimates have shown that blood pressure
and some of its components, fasting blood sugar, triglycerides and waist circumference were
mainly due to environmental factors with some genetic components. However, high cholesterol,
insulin, body mass index and body fat were mainly due to genetic factors.
Conclusions
The major health problems identified were the high prevalence in adults of hypertension and the
metabolic syndrome. Most importantly was the high prevalence of borderline hypertension and
prediabetes in young subjects as well as the alarmingly high prevalence of high cholesterol in all
subjects. According to heritability analyses, lifestyle innovations can be instrumental in preventing
or delaying hypertension, prediabetes, diabetes and the metabolic syndrome, especially in young
subjects. Medical intervention is, however, required for the management of high cholesterol.
Further studies, such as the Ministry of Health's non-communicable disease health initiative
(NCDI) program, are required to determine if the above findings apply to the whole of Oman
Bioactivity-Driven Chemical Investigation of Omani Biodiversity for
Medicinally and Agronomically Valuable Compounds: The Development of
Omani Natural Products
Project Code:
Funds:
Funding Source:
Start Date:
Duration:
Team Members:
(SR/SCI/CHEM/01/01)
213,000 OMR
His Majesty’s Trust Fund
02 May 2001
5 years
Researchers
Dr. Majekodunmi Fatope (P.I.)
Dr. Abdulrahman Abdulnour,
Dr. Salma Mohammed Al-Kindy
Dr. John William
Dr. Mike Deadman
Dr. Fakhr Suliman
Dr. Abdulkhadir Elshafie
Dr. Shahina A. Ghazanfar
Research Assistants
Mr. Salim Humaid Al-Saidi
Dr. John Ochei
Ms. Suad Khamis Al- Burtamani
Ms. Ramlah Saud Al Mahrooqi
Ms. Wafa Mohamed Al-Shuaily
Dr. Yousif Mohamed Al-Maqbali
Postdoctoral Fellows
Dr. Ruchi Gulati Marwah
Dr. Anthony Onifade
Dr. Cheng Jun
Executive Summary
Objectives
To investigate plants and microbes for natural products that could have uses in medicine and
agriculture.
Methods
Sixty plants from 30 families and four fungi from 48 strains were subjected to activity-guided
characterization of their secondary metabolites. They were investigated because of their local
uses or performance in antibacterial, antifungal, toxicity and anti-oxidant tests. The chemical
composition of the essential oils from 14 of the plants, used as fragrant disinfectant or insect
13
repellent, were determined by C-NMR, GC-MS and GC-FID analyses and tested for activity.
Results
The fragrant oils of the plants demonstrated good anti-fungal, anti-bacterial and insecticidal
properties. For example, the essential oil of Plectranthus cylindraceus inhibited the growth of
Klebsiella pneumoniae, Staphylococcus aureus, Bacillus subtilis and Candida albicans with mic
-1
values in the range 7.6-62.5 mg ml , and the growth of Microsporum gypseum, Trichophyton
rubrum, Alternaria alternata, Curvularia lunata, Fusarium oxyporum and Stemphylium solani for
-1
about a week at 250 mg m1 . A combination of the oils of P. cylindraceus and Haplophyllum
-1
tuberculatum (1:1) was lethal to Meloidogyne javanica, its larvae, and eggs at 12.5 mg ml and
-1
offered protection against root-knot nematode at 2.5 and 5.0 mg of oil ml of soil. The fragrance
and insecticidal essences of P. cylindraceus, Anethum graveolens, Ocimum spp, Cleome spp, H.
tuberculatum, Pluchea arabica were identified as dillapiole, limonene, estragole, linalool,
carvacrol, caryophyllene oxide and cadinol. The structures of antifungal compounds isolated from
Blepharispermum hirtum, Withania qaraitica, P. arabica and Commiphora wightii were assigned
from spectra data. Isolates from the plants studied were more anti-fungal than anti-bacterial
except for W. qaraitica whose antibacterial agent was identified as withaferin. B. hirtum gave a
terpenoid that was anti-fungal to dermatophytes at very low concentration. Of the 10 edible plants
investigated, Carralluma plants have no proven health benefits, but could serve as raw material
for the production of pharmaceutical steroids. Acalypha indica and Allophyllus rubifolium are
edible vegetables that could have health benefits.
Conclusions
A number of lesser-known high oil-yielding plants with antimicrobial and antifungal properties
were identified. They produce oils which can be incorporated into shampoos, soaps, perfumes,
pesticides and fragrant hydrosols. Fungal metabolites are attractive sources of pharmaceutically
useful antibacterial and antifungal agents, but investigations of plants for bioactive compounds
will continue to be one of the bases for understanding cultural practices in Oman as far as the
herbal treatment of certain diseases or control of degenerative ailments through edible
vegetables are concerned.
Improvement of Date Palm Production and Date Quality
Project Code:
Funds:
Funding Source:
Start Date:
Duration:
Team Members:
(SR/AGR/PLNT/01/01)
167,844 OMR
His Majesty’s Trust Fund
02 May 2001
4 years
Researchers
Dr. Mahdi ElMardi (P.I. deceased)
Dr. Khaja Mohamed Azam,
Dr. Michael Deadman
Dr. Fahad Al Julunda Al Said
Prof. Humphrey Esechie
Dr. Osman Mahjoob Gafar
Dr. Isam Kadim
Dr. Stefan Kasapis
Dr. Hayder Abdelrahman
Dr. Salim Ali Al-Rawahi
Dr. Linus Opara
Dr. Mohammed Sahriur Rahman,
Dr. Khalifa Al Kiyumi
Research Assistants
Ms. Latifa Mohammed Al-Kharusi
Mr. Ali Ahmed Al-Raeesi
Mr. Yousif Mohamed Al-Maqbali
Mr. Ibrahim Al-Rahbi
Mr. Naseeb Musabah Al-Saqri
Ms. Insaf Mohamed Al-Marhubi
Mr. Abdullah Said Al-Belushi
Dr. Ahmed Sailm Al-Busaidi
Mr. Harith Saleh Al-Nabhani
Mr. Amer Al Barhi
Mr. Khaled Al-Mihrazi
Mr. Ahmed Al-Shidi
Executive Summary
Objectives
The project aimed to improve date yield and quality through tree management, pest and disease
control; to enhance date quality through improved harvest and post-harvest techniques and
maximize returns by developing date by-products of commercial value.
Methods
A survey was conducted to identify suitable palm orchards. Irrigation and fertilization requirement,
type of mulch, growth rate, fruit yield/quality and water requirements were investigated to
determine the best practices that can improve tree productivity. Pollination methods, thinning,
bunch-bending, fruit yield and quality, male/female cultivar-compatibility as well as size, shape
and ripening of fruits were investigated. Pesticide doses and frequency of application as well as
biological control were determined. The appropriate fruit-stage to harvest and the best harvesting
methods were determined. The effect of date preparation procedures on storability and the quality
of dates, and the application of the appropriate method for artificial ripening were determined. The
physics of date components that optimize food texture and process technologies was determined.
Nutritive value of date by-products were studied by various techniques. Date by-product feed
rations were fed to Omani animals and their effects on performance and health were evaluated.
Results
Irrigation and fertilizer experiments revealed that traditional irrigation-system methods need to be
modernized. Application of organic matter alone is not enough to generate good yield and quality
dates. A bubbler irrigation system at 200 l/day supported by mulching with date palm fiber is
ideal. Chemical fertilizer, especially NPK, increased the yield and improved the quality of dates.
The recommend amounts for 7-8 year-old palms are 1000g urea, 500g triple super phosphate
and 800g potassium sulfate to be supplemented with micronutrients. Mechanical pollination was
preferred over hand pollination. Date fruits in the bisir stage can be stored frozen for 7-8 months
or less as desired and ripened by thawing, heating and drying. The tamr stage can be improved
by immersing fruits in sugar solution to minimize shrinking and wrinkling. Dubas bug poses the
most serious challenge to date palm production in the Sultanate and aerial spraying to control it
should be re-evaluated. The second important pest is red palm weevil. A new date candy was
developed using ten Omani date varieties, exploring the possibilities of utilizing what is
considered to be varieties of high quality dates and comparing that with other varieties of inferior
quality.
Conclusions
The project defined various approaches in improving date palm production and date quality,
including the establishment of baseline data for products and diseases to be used in extension
activities and the development of potential small-medium scale enterprises. If results of the
project on disease control, production efficiency, post-harvest technology, and recommendations
for marketing are put into practice, date production is expected to further contribute to growth and
diversification of Oman’s economy.