Study the Effect of High Sensitive-C reactive protein in newly Diagnosed Acute Myeloid Leukemia with other Hematological markers

 

Fatma Abdalhamza Obed1, Noorhan Khalid Shafeeq2, Raghda Shams Akram3,

Elaf Zuhair Hmeed4

1Hematological Center, AL-Mustansiriya University, Baghdad, Iraq.

2Department of Chemistry/ College of Education, For Pure Science (Ibn-Al-Haitham)

University of Baghdad. Iraq.

3Department of chemistry and Biochemistry, College of medicine, Mustansiriyah University, Baghdad, Iraq.

4Hematological Center, AL-Mustansiriya University, Baghdad, Iraq.

*Corresponding Author E-mail: aliomran662000@yahoo.com, noorhan.albayaty@gmail.com

 

ABSTRACT:

Acute myeloid leukemia (AML) is a clonal disease that manifests itself in the bone marrow as a hyper proliferative immature myeloid cells with a defective differentiation program. In adults, Acute leukemia is the most frequent type of cancer. The most common causes of death among patients include severe infections, resistance, and relapses. Recent research has suggested that the disease is caused by a collection of hematopoietic stem cell mutations accumulated over time. the study was carried out to detect how high sensitive C-reactive protein (hs-CRP) affected newly diagnosed Acute Myeloid Leukemia patients with other co morbidity and diabetes insipidus.in Conclusion; Increased high sensitive (c-reactive protein) (hs-CRP) could be act as predictive factor in individuals with diabetes and other hematological changes who have acute myeloid leukemia. Aim of study: the study was carried out to detect how high sensitive C-reactive protein (hs-CRP) affected newly diagnosed Acute Myeloid Leukemia patients with other co morbidity and diabetes insipidus. Conclusion: Increased high sensitive (c-reactive protein) (hs-CRP) could be act as predictive factor in individuals with diabetes and other problem who have acute myeloid leukemia. Furthermore the causes between association with diabetes insipidus are not understood.

 

KEYWORDS: Acute myeloid leukemia.

 

 


INTRODUCTION: 

Acute myeloid leukemia (AML) is a clonal disease that manifests itself in the bone marrow as a hyper proliferative immature myeloid cells with a defective differentiation program1,2. Despite advances in acute leukemia therapy and higher percentages of high percent of healing following induction of treatment, Many people are at risk of relapsing and dying from the disease. In adults, Acute leukemia is the most frequent type of cancer. The most common causes of death among patients include severe infections, resistance, and relapses3. AML, which was once considered incurable, is now cured in roughly 35–40% of people under the age of 604.

 

 

For those over 60, the prediction is improving but it is still difficult. Recent research has suggested that the disease is caused by a collection of hematopoietic stem cell mutations accumulated over time. A phenomena known as clonal evolution has been defined using deep sequencing techniques on primary and recurrent malignancies, with each founding clone and novel subclones altering the healing approach5. (AML) and diabetes insipidus (DI) are extremely uncommon, approximately about 100 case reports have been published last decades. While the description of relation between leukemia and diabetes insipidus for first time dating back to 19706 while early publication of this study was released in 19847, the underlying pathophysiology was not clear. that some research attributed this relation to monosomy7, inversion (q21q26) and an weak effect of chemotherapy leads to this complication6. High sensitive (C-reactive protein) (hs- CRP), a plasma protein generated and secreted mostly by the liver in response to cytokines released by tumor microenvironment such as leukocytes, immune cells, signaling molecules8. Blast cell proliferation could trigger an inflammatory response by raising (CRP) levels. Special blood test to detect the very low level CRP (hs-CRP), As part of the innate immune response, which represent acute phase serum protein that rises as first response to inflammation. It has both pro inflammatory and anti-inflammatory properties9. As a result, in rare cases, the CRP may exacerbate tissue damage. Chronic inflammation, on the other hand, may play a role in the development of cancer9. HS-CRP is an inflammatory marker that plays a direct function in the development of cancer. The half-life of serum hs-C reactive protein is 19 hours. The link between CRP levels and the chance of getting cancer in people with acute myeloid leukemia, as well as how that risk is influenced by a variety of factors8.

 

MATERIAL AND METHODS:

Acute myeloid leukemia (AML) patients a composed sixty patients (30 male, 30female).The average age of patients was (39.08±12.31)years (range 25-55). There were 30 as control group (16 male and 14 female) and the average age of control group was( 34.11±8.12) years range. This study done in national center of hematology and national Diabetes Center/Al-Mustansiriya University during the period from December 2018 until the end of April 2019. All subjects had to go through clinical examination to determine existence of other disease, some tests as complete blood a count( hemoglobin, platelet, and white blood cell), ferritin, serum blood sugar ,total cholesterol, (TC) and other lipid profile, urea, serum creatinine. glutamate oxaloacetate transaminase (GOT) and, glutamate pyruvate transaminase(GPT) measured by Backmem Coulter (Au480).

 

The enzyme linkage immunosorbent assay was used to assess high sensitive c reactive protein (hs-CRP). (ELISA kit of BioSource, Cat No:MBS040244)

 

RESULT:

Hematological and biochemical parameters of acute myeloid leukemia diagnosed are illustrated in table (1). There was high significant in white blood cell, and high sensitive (c- reactive protein) in acute myeloid leukemia (AML) in comparison to the control group. In acute myeloid leukemia (AML), Fasting blood glucose (FBG) and total cholesterol levels both increased significantly (TC), triglyceride (TG), and urea When compared to the control group, there were significant declines in hemoglobin (Hb) and platelet (plt). In acute myeloid leukemia, there was no significant difference in Creatinine, GOT, or GPT when compared to the control group (AML).

 Table (2) shown a significant increase of Hb, plt, TC, TG and hs-CRP in male and female acute myeloid leukemia (AML) patients (P=0.05), and a high significant increase, of Wbc in female acute myeloid leukemia (AML) when compared with male acute myeloid leukemia (AML) , while a high significant decreased of ferritin in female acute myeloid leukemia (AML) when compared with male acute myeloid leukemia (AML) . Also there was no significant shown of FBG , urea, creatinin, GOT and GPT between male and female acute myeloid leukemia (AML) patients.

 

Table (3) demonstrated that There was a strong positive link between has (CRP) and HB, plt, Wbc, ferritin, FBG and TG in male and female acute myeloid leukemia (AML) patients, and a high positive correlation between hs-CRP and TG in male and female acute myeloid leukemia (AML) patient, while no correlation was shown between hs-CRP and TC, HDL, urea, creatinin, GOT and GPT in male and female acute myeloid leukemia (AML) patient.

 

Table (1): Hematological and biochemical parameters in newly diagnosed acute myeloid leukemia (AML) as well as control group

(P-value)

(Control)

n(30)

(AML)

n(60)

Parameter

mean±SD

 mean±SD⃰

0.05

13.7±1.12

11.6±1.66

Hb, (g/dl)

0.001

296.2±28.3

39.6±8.3

Plt,(103/µl)

0.01

8.22±2.03

26.7±1.45

Wbc, (103/µl )

0.01

86.1±12.4

36.4±8.76

Ferrtin (ng/ml)

0.05

89.4±11.32

127.4±22.5

FBS, (mg/dl)

0.05

171.3±28.2

217.5±52.4

Tc, (mg/dl)

0.05

110.3±15.4

168.4±13.4

TG (mg/dl)

0.216

47.6±7.8

45.5±8.21

HDL (mg/dl)

0.05

26.3±10.2

48.4±11.6

Urea (mg/dl)

0.320

0.75±0.18

0.73±0.21

Creatinin (mg/dl)

0.163

38.3±12.3

40.0±21.6

GOT (mg/dl)

0.127

30.9±7.98

36.6±10.1

GPT (mg/dl)

0.001

12.6±5.2

22.4±6.41

hsCRP (ng/ml)

⃰⃰⃰ standard deviation.

 

Table (2): Hematological and biochemical parameters between male and female acute myeloid leukemia (AML) patients.

(P-value)

Female

No(30)

Male

No(30)

Parameters

mean±SD

mean±SD⃰

0.05

9.32±0.33

12.0±1.80

HB (g/dl)

0.05

30.10±3.11

49.5±5.41

Plt(103/µl)

0.01

16.6±0.51

10.8±1.40

Wbc (103/µl )

0.001

15.2±8.19

21.7±17.0

Ferrtin (ng/ml)

0.320

124.2±10.4

127.3±8.61

FBS (mg/dl)

0.05

198.4±51.2

264±65.4

Tc (mg/dl)

0.05

160.23±1.2

176.5±14.6

TG (mg/dl)

0.132

46.2±5.21

44.9±10.4

HDL (mg/dl)

0.42

26.3±11.8

22.4±9.7

Urea (mg/dl)

0.15

0.72±0.43

0.83 ±0.32

Creatinin (mg/dl)

0.29

32.5±7.10

39.3±3.01

GPT (mg/dl)

0.23

42.0±24.3

38.0±17.3

GOT (mg/dl)

0.51

28.9±3.01

16.86±3.40

hsCRP (ng/ml)

⃰⃰⃰ standerd deviation.

 

Table (3): Correlation coefficient between hsCRP levels and all parameters in both gender (male and female) acute myeloid leukemia (AML) patients.

hsCRP

Parameters

Female

Male

R

R

0.240*

0.034*

Hb (g/dl)

0.216*

0.430*

Plt(103/µl)

0.224*

0.109*

Wbc (103/µl )

0.084*

0.038*

Ferrtin (ng/ml)

0.243*

0.125*

FBS (mg/dl)

0.038

0.029

Tc (mg/dl)

0.085**

0.052**

TG (mg/dl)

0.103

0.079

HDL, (mg/dl)

0.182

0.011

Urea, (mg/dl)

0.062

0.009

Creatinin, (mg/dl)

-0.091

-0.142

GOT (mg/dl)

0.360

0.235

GPT (mg/dl)

R valu:- the strength and direction of a relationship between variables

 

DISCUSSION:

Immunological microenvironment play important role in growth and outcome of Acute myeloid leukemia by the release of inflammatory reactant protein specially c-reactive protein10. Acute myeloid leukemia affect people at any age but its uncommon before the age of 45years,and the average age of first diagnosis about 68. Its significance has developed with an aging population 11,12 has been postulated for long time, and numerous clinical attempts have been made in, this field11. In this study shown, There was a high significant increased in white blood cell. While low significant decreased in Hb, (PLT) and ferritin, in acute myeloid leukemia (AML) when compared with control group, this is agreement with this study13,14,15. This can be demonstrated by the truth that in leukemia there is a clonal proliferation of malignant cells that may arise during any step of maturation in the bone marrow involving myeloid, lymphoid, or pluripotent stages16, also a high sensitive c- reactive protein in acute myeloid leukemia (AML) when compared with control group this is agreement with this study17. Table 1 depicts a significant increase in fasting blood glucose, (FBG), total cholesterol, (TC), and triglyceride levels, (TG) and urea in acute myeloid leukemia (AML) when compared with control group, This could be linked to malignant cells' high metabolic rates, as well as body mass reduction, which causes fat substance to be removed from cells, lowering (BMI). Chronic exposure to environmental contaminants may contribute to the progression of diabetes by causing metabolic imbalance. Hypercortisolemia resulted from chronic stimulation of hypothalamic-pituitary axis result in metabolic imbalance in stored energy redistribution. 18,19. In addition, renal damage that affect about 48% of patients with acute myeloid leukemia ,this result is in agreement with what stated in (Najjar et al), 2017 report, where the renal failure usually because of hypocalcaemia and light chain nephropathy8. Furthermore no significant was shown in table (1) of creatinin, (GOT) and (GPT) in acute myeloid leukemia (AML) when compared with control group this is agreement with Gengiz et al study15. Table (2)/ shown a significant increase of Hb, plt, TC, TG and hs-CRP in male when compared with female acute myeloid leukemia (AML) patients (PV=0.05), and high significant increase of (Wbc) in female acute myeloid leukemia (AML) when compared with male acute myeloid leukemia (AML), while a high significant decreased of ferritin, in female acute myeloid leukemia (AML) when compared with male acute myeloid leukemia (AML), These findings matched those of other researchers study that detect high serum ferritin in newly diagnosed and in remission patient with leukemia for both sex, suggesting that leukemia cells may alter iron metabolism, resulting in iron overload8. In addition more increasing in (hs-crp) in male patients because of the response to tumor necrosis, local tissue damage, or associated inflammation20. modifications in blood lipids in the case of acute leukemia, which have revealed a considerable change in lipid profile when compared to healthy people, which is consistent with21 findings. Einollahi et al, studied the serum lipids changes in leukemia and lymphoma22 the cholesterol and triglyceride levels is high in male when compared with female AML before treatment in Previous studies in Einollahi et al study have shown that leukemic blood and bone marrow cells from (ALL) patients can uptake (HDLC) with a higher rate than normal cells, Moreover, their findings suggest that lipid profiles are altered in response to leukemia activity22,23. there was no significant shown of FBG between male and female acute myeloid leukemia (AML) patients. while The pathogenesis of diabetes insipidus in AML people is uncertain. The pathophysiology has been documented to include a leukemic infiltration in the hypothalamus-pituitary area, and our case exemplifies this etiology. Postmortem examinations have revealed Pere pituitary leukemic infiltrates in AML individuals who did not have symptomatic diabetic insipidus24.

 

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Received on 25.02.2022             Modified on 07.04.2022

Accepted on 14.05.2022           © RJPT All right reserved

Research J. Pharm. and Tech 2023; 16(1):119-122.

DOI: 10.52711/0974-360X.2023.00022