Iraqi Journal of Hematology

Abstract:
Chronic myeloid leukemia (CML), as the name suggests, is a chronic disorder in which granulocytes
undergo dysregulated production and uncontrolled proliferation. Majority of CML patients present
during the chronic phase (CP) of the disease. The interval from CP to onset of blastic transformation
and acute leukemia can vary from days to several years. The biological basis of blast phase is
poorly understood. Most common blast crisis is myeloid type and less frequently lymphoid or
promyelocytic. The transformation of CML to promyelocytic blast crisis is a rare form. These findings
suggest that BCR‑ABL1 gene arises from leukemic stem cell (LSC) which is still not committed to
myeloid or lymphoid differentiation. The blastic clone may originate either at the multipotent LSC
or at committed leukemia progenitor cell. Here, we report a case of promyelocytic blast crisis with
t(15;17) in addition to t(9;22).

BACKGROUND: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a highly
variable clinical course and outcome. Many clinical and biological characteristics have been used to
classify patients with CLL into different subgroups of variable prognosis. Many studies have reported
that in CLL, the interaction between pro‑ and antiapoptotic BCL2 family members influences the
sensitivity to cytotoxic drugs and affects survival and overall outcome.
OBJECTIVES: The aim of the study was to assess BCL2 and BAX expression and BCL2/BAX ratio
relation to other known prognostic markers (Binet stage, absolute lymphocyte count, lymphocyte
percentage in bone marrow [BM], and ZAP‑70 and CD38 expression).
PATIENTS AND METHODS: The study analyzed the expression of BCL2 and BAX, BCL2/BAX
ratio, and ZAP‑70 in the BM biopsy of 42 randomly selected CLL patients.
RESULTS: BCL2 was positively expressed in 92.9% of CLL cases, significantly associated with Binet
stage of disease (P = 0.04), ZAP‑70 (P = 0.001) but not with CD38, and also significantly correlated
with absolute lymphocyte count (P = 0.015) and lymphocyte percentage in BM (P = 0.017). BAX was
positively expressed in 64.3% of CLL cases; there was no significant association between BAX with
Binet or with other assessed prognostic factors (except with ZAP‑70, P = 0.001). BCL2 and BAX
were significantly correlated with each other (P = 0.001). BCL2/BAX ratio was not associated with
any prognostic parameters we assessed.
CONCLUSION: We may conclude that we may consider BCL2 as simple informative tool to assess
disease activity while BAX and BCL2/BAX ratio alone are of no prognostic value in prediction of
disease course.

Abstract:
BACKGROUND: Cardiac complications are still the primary cause of mortality and a major cause
of morbidity in thalassemia patients.
OBJECTIVES: The aims of this study were to assess the prevalence of cardiac involvement in TDT
and NTDT beta thalassemia patients and compare between the different forms and severity in both
groups.
MATERIALS AND METHODS: In this prospective study, 70 TDT and 50 NTDT β‑thalassemia patients
were recruited; their cardiac status was evaluated by transthoracic echocardiography as per the
standard recommendations. Patients’ cardiac status was evaluated against the causal risk factors.
RESULTS: The mean serum ferritin level was significantly (P < 0.001) higher in the TDT patients
(4940 ± 3643 ng/mL) compared to the NTDT patients (634 ± 520 ng/mL). The mean hemoglobin
was significantly (P = 0.004) higher in the TDT group (9.2 ± 0.8 vs. 8.7 ± 1.0 g/dL). The prevalence
of dilated cardiomyopathy and left cardiac dysfunction in TDT was 18.6%, whereas pulmonary
hypertension (PHT) was found in 30% of NTDT patients.
CONCLUSION: Dilated cardiomyopathy was prevailing in the adult TDT patients, whereas PHT was
the main cardiac complication in NTDT patients.

Abstract:
BACKGROUND: Thromboembolism is a complex disease caused by different acquired and
inherited factors. The common mutations including Factor V leiden (FVL), prothrombin (PTG), and
methylenetetrahydrofolate reductase (MTHFR) are important inherited causes in both venous and
arterial thrombosis.
OBJECTIVES: The aim of this study was to determine the frequency of the common three
thrombophilia mutations in a group of patients with unstimulated thrombosis in comparison to healthy
controls.
PATIENTS AND METHODS: This is a prospective case‑control study of mutations in 100 samples,
50 patients with documented thrombosis referred to the Sulaymaniyah Public Health Laboratory for
thrombophilia screening, as well as other 50 healthy age‑matched controls. Multiplex polymerase
chain reaction and reverse hybridization to oligonucleotide‑specific probes, was used to detect FVL
G1691A, PTG20210A, and MTHFRC677T mutations. Assays for other thrombophilia markers (Protein
C, Protein S, and Antithrombin) were also performed.
RESULTS: FVL was found in 22% of patients versus 6% of controls and associated with a 4‑fold
increased risk of thrombosis OR: 4.41, P = 0.021. MTHFR and PTG were found in 42% and 4%,
respectively among patients with no significant increased risk. Mutations with more than one
thrombophilia markers further increased the risk of thrombosis to 5‑fold P = 0.025. Deep‑vein
thrombosis was the most common form of thrombosis and it is more in a young age group.
CONCLUSIONS: FVL is significantly related to the risk of thrombosis development and presence
of other thrombophilia markers further increase thrombotic risk, so understanding these facts may
encourage screening those patients and may help proper management.

Abstract:
BACKGROUND: Chronic inflammation has been suggested to contribute to the pathogenesis of
thrombosis in polycythemia vera (PV) as it triggers in vivo activation of platelets, leukocytes, and
endothelial cells, which are all of major importance during thrombus formation.
OBJECTIVES: The aims of this study were to evaluate the pathophysiology behind increased
thrombosis in PV in terms of the effect of JAK2V617F gene mutation copies in relation to the intensity
of the heat.shock proteins 70 (HSPs70) and long pentraxins.3 (PTX.3).
SUBJECTS AND METHODS: Thirty patients with PV, 23 with secondary polycythemia, and thirty
healthy volunteers were studied. Hemoglobin level, packed‑cell volume, white and red blood
cells count, mean corpuscular volume, and platelet counts were estimated. The enzyme‑linked
immunosorbent assay was used to estimate the HSP70 and PTX‑3 levels, whereas the real‑time
polymerase chain reaction technique for the assessment of the JAK2 mutation rate was done for
only thirty PV patients.
RESULTS: Significantly higher HSP70 and PTX‑3 levels were detected in PV patients. A positive
relationship was demonstrated between the JAK2 mutation rate and each of HSP70 and PTX‑3 and
between the latter two biomarkers.
CONCLUSION: The elevated HSP70 and PTX‑3 concentrations and the clear relationship between
them and JAK2 mutation rate can drive the procoagulant activity in blood cells in patients with PV.

Abstract:
BACKGROUND: Chronic lymphocytic leukemia (CLL) is a monoclonal disorder characterized by
relentless accumulation of monoclonal B‑cell. Beta‑2 microglobulin (β2m) is an extracellular protein
that is bound to the chain of Class 1 major histocompatibility complex molecule, which is present
on all nucleated cells. Interleukin‑4 (IL‑4) is a T‑cell‑derived pleiotropic cytokine which is involved
in the mechanism of survival of leukemic B‑cell. IL‑6 is a pleiotropic cytokine produced in the site
of inflammation; it plays a major role in the acute‑phase response. β2m, IL‑4, and IL‑6 may have
prognostic value in patients with CLL.
OBJECTIVES: The aims of this study were to estimate the levels of β2m, IL‑4, and IL‑6 in different
stages in patients with CLL and to know if there is prognostic significance of β2m, IL‑4, and IL‑6 in
those patients.
PATIENTS AND METHODS: This study was conducted on fifty patients from March 2013 to March
2015 including 36 males and 14 females; all were newly diagnosed CLL. Those patients were
divided into two groups depending on the stages of disease: Group I (21) patients and Group II (29)
patients according to the Rai staging system. Diagnosis of CLL was determined for all those patients
by complete blood count and blood films and flow cytometry. The estimation of β2m, IL‑4, and IL‑6
was done by enzyme‑linked immunosorbent assay technique.
RESULTS: The male‑to‑female ratio was 2.3:1; there were 29 (58%) patients in Group I (Rai Stages
0, I, and II) and 21 patients (42%) in Group II (Rai Stages III and IV). β2m, IL‑4, and IL‑6 were elevated
in patients with advance stage of the disease as the levels of these prognostic markers was higher
in Group II compared to Group I.
CONCLUSION: The elevation of β2‑m, IL‑4, and IL‑6 indicates bad prognosis of the disease and
poor outcome because the serum level of β2m, IL‑4, and IL‑6 is increased in the advanced stages
of the disease.

Abstract:
BACKGROUND: Sickle cell disease is a monogenic disease with heterogeneous clinical course.
Many genetic factors such as inheritance of α‑thalassemia trait and fetal hemoglobin (Hb) level,
related to the presence of specific haplotypes, are among the factors that modify disease severity.
OBJECTIVES: To identify βS haplotypes of children with sickle cell anemia (SCA) in Basra and
assess the association of clinical variables and hematological parameters with different βS haplotypes.
PATIENTS AND METHODS: This analytical cross‑sectional study included 62 patients with SCA
registered at Basra Center of Hereditary Blood Disease. In addition to clinical data, blood samples
were obtained for complete blood count, lactate dehydrogenase and polymerase chain reaction,
and Sanger sequencing analysis of HBB gene. Statistical analysis was done using SPSS program
version (23) software.
RESULTS: The mean age of studied patients was 7.15 ± 3.81 years, with a male to female ratio
of 1:1.7. The most common haplotype was the Arab Indian (AI) in 34 (54.8%) patients, followed
by Benin and Senegal haplotypes in 12 (19.4%) patients for each, and an atypical haplotype in
4 (6.5%) patients. No significant differences were found in the mean age of diagnosis, the frequency
of vaso‑occlusive crises, blood transfusions and hospitalizations among patients with different βS
haplotypes, P > 0.05. However, patients with AI haplotype have significantly higher Hb, red blood
cell count, hematocrit and fetal Hb compared to other haplotypes, P < 0.05.
CONCLUSIONS: The AI is the most common haplotype among SCA patients from Basra and it was
associated with significantly higher Hb, hematocrit, and fetal Hb levels.

Cancer represents one of the most up to date issues worldwide because of the increasing number of
affected people and the impact of it on the families and health system. It is one of the new challenges
that face scientists and health worker and for many years lots of research and trials were trying to help
in fighting this killer. The main aim of this review is to get a general look at the new understanding of
cancer pathways and possible causes of resistance and their application in trails and clinical works,
this piece of work aims to highlight the importance of pathophysiology of cancer in producing an
effective treatment through targeting them. This review depended mainly on reviewing articles in the
PubMed and Google Scholar, through writing (The hallmark of cancer, Hanahan and Weinberg) in
the PubMed, around 14 articles had been emerged and only articles produced by the same authors
in the years 2001 and 2011 had been selected as they were talking about the hallmark of cancer
and resistance in details. Then, each pathway was followed as we searched according to a specific
pathway and its targeted therapy in the PubMed and Google Scholar. Around 60 articles and trials
had proved that targeting these pathways at different levels and even trying to stop these pathways
with different targets can help to control cancer, and the new studies showed very promising results
and they opened the door for future studies. For long time it was believed that cancer cells share six
characteristic between them to develop and growth, however the same researchers who developed
the initial hallmark of cancer had added new hallmarks which are : (1) abnormal metabolic pathways,
(2) evading the immune system and two enabling characteristics: (1) genome instability, and (2)
inflammation. Targeting these pathways has improved survival dramatically in most of cancers.

Abstract:
BACKGROUND: Deficiency of iron is one of the most prevalent nutritional disorders, and obesity
is an increasing nutritional problem, but only a few studies mention a possible association between
them in Iraq. Adipocytes secrete adipokines, some of them are related to the inflammatory response
in addition to hepcidin, a hormone that mediates iron metabolism.
OBJECTIVES: This study aimed to assess the significance of serum hepcidin in obese patients
with iron deficiency.
PATIENTS MATERIALS AND METHODS: Ninty patients were separated into Group 1 (normal
weight), Group 2 (30 overweight), and the Group 3 (30 obese). All patients were investigated by
complete blood count, serum hepcidin, iron, total iron‑binding capacity, and ferritin using the standard
laboratory techniques.
RESULTS: There were no significant differences among the groups regarding the severity of
anemia, red cell indices, white blood cells, and platelets count. The obese group had significantly
higher serum hepcidin and ferritin (P = 0.003, 0.040, respectively), while serum iron is lower. Serum
hepcidin positively correlated with the serum ferritin but inversely correlated with serum iron. Increased
hepcidin level in obesity could be related to inflammatory adipokines that effect on hepatic hepcidin
transcription and hepcidin mRNA expression, in addition to the nonhepatic production of hepcidin in
an autocrine manner; hepcidin, in turn, is responsible for low serum iron, but a high ferritin level in
correlation to high hepcidin may explain by low‑grade chronic inflammation associated with obesity.
CONCLUSIONS: The severity of iron‑deficiency anemia is not affected by body weight; however,
significantly higher serum hepcidin and ferritin in the obese patient with a lower serum iron should
be considered during the assessment of iron status in those patients.