| Abstract |
Introduction: Insufficiency or deficiency of carnitine has been found in a number of physiological and
pathological situations. Individual studies in cancer patients showed a secondary carnitine deficiency,
which may be the result of metabolic changes arising directly or indirectly from chemotherapy or
from the actual process of the tumor itself. A decrease in oxidation of fat is expected when
deficiency of carnitine occurs. Consequently beta-oxidation is reduced and as result glycolysis
increases, favoring the growth of tumor cells, which draw energy from glycolysis.
Aim: This thesis was designed to study the alterations of carnitine and its fractions in children with
acute leukemia, the probability of insufficiency of carnitine which could arise in these patients, the
degree and duration of this insufficiency as their impact in the clinic process and final outcomes of
patients. Patients’ characteristics such as age and sex, somatometric features, peripheral blood
parameters, serum biochemistry and risk groups for the disease were also examined. Comparison with
healthy controls from the same geographical area was also performed.
Patients and methods
The study population included forty children and adolescents (12 females and 28 males) diagnosed
with acute leukemia in the Pediatric Hematology/Oncology Department of our Hospital. The patients
received treatment according the BFM-ALL and AML protocols. Thirty seven patients were diagnosed
with ALL (Acute Lymphoblastic Leukemia) and three patients with AML (Acute Myelogenous
Leukemia).
Serum samples and somatometric parameters were examined in four different phases of the disease:
Phase A: at the diagnosis, phase B: one year after initiation of chemotherapy, phase C: at the end of
therapy and phase D: months to years following completion of therapy.
The SPSS 15.0 software package was used for the calculations. P &λτ 0.05 was considered as
statistically significant.
Results
The mean values of acylcarnitines, free carnitine, total carnitine, and ratio acyl/free per phase for
patients and contol group appears in table 1.
Comparison between all phases was performed regarding the values of Carnitine free, total and ratio
acyl /free. Statistically significant decline in values of carnitine free and total has been observed
between phase A and phase B (P=0.023) and (P=0.023) respectively. Statistically significant changes
also were observed between the phase B and D for both free (P=0.054) and total carnitine (P= 0.035).
Between the other phases statistically significant changes were not observed. The ratio acyl/free
was not statistically significant changed between the phases.
Statistically significant correlations were found between the alanine and lactate in phase A (P =
0.000), phase C (P = 0.009) and phase D (P = 0.000). A statistically significant correlation between the
alanine and lactate with free fatty acids was observed only in phase D (P = 0.001 and P = 0.000)
respectively.
Table 1
Conclusions: In the present study insufficiency of carnitine was not observed although a statistically
significant decrease in carnitine levels was found within different phases of the disease especially
during induction and consolidation treatment (phase A-B) for both free & total carnitine (p=0.023).
The decrease in carnitine levels free and total was transient and was reversed after the end of
chemotherapy p= 0.054 and 0.035 respectively. The abatement found is not correlated with
nutritional status, age, gender, risk group of the disease, or hemoglobin levels. Patients with higher
BMI z-score after the first year of treatment tend to have a better disease course and prognosis.
Long term follow up of these patients may allow a more precise correlation of the decrease in levels
of carnitine found in our study with late effects of leukemia and chemotherapy.
Further studies may elucidate the impact of this decrease in carnitine’s levels in prognosis and final
outcome of the disease as well as the potential benefit from supplementation of carnitine during
chemotherapy.
years
Free carnitine
μmol/L
Total carnitine
μmol/L
Ratio
acyl/free
Phase A 40 6.3+3.912
(2,02 - 16,39 )
45.6 + 18.031
(18.8-100.6)
54.1 + 22.961
(22.2-142)
0.188 + 0.128
(0.073-0.674)
Phase B 39 7.2 + 3.832
(2.9 – 17.1)
36.2 + 17.872
(2.6-115.8)
43.1 + 18.942
(5-124.5)
0.229 + 0.160
(0.052-0.894
Phase C 38 8.7 + 3.467
(3.8 – 17.6 )
40.2 + 12.582
(24.3-76.6)
48.7+ 13.711
(28.9-85.9)
0.208 + 0.104
(0.094-0.615)
Phase D 32 10.9 + 3.412
(6.7- 18.9)
42.9+ 8.077
(27.2-65)
51.6 + 12.995
(33.7-107.7)
0.197 + 0.981
(0.114-0.656)
Control
group
30 11.86 + 4.057
(range 5-18y)
37.9 + 5.121
(range 28-46)
46 + 6.533
(range 35-58)
0.215 + 0.575
(0.108-0.330)
5
Σύμβολο Επεξήγηση
AC ακυλ καρνιτίνη
FC ελεύθερη καρνιτίνη
TC ολική καρνιτίνη
ATP αdenosine triphosphate, τριφωσφορική αδενοσίνη
GTP γουανο τριφωσφορική αδενοσίνη
CoA συνένζυμο Α
VLDL very low density lipoproteins, πολύ χαμηλής πυκνότητας λιποπρωτεϊνες
ΟΛΛ οξεία λεμφοβλαστική λευχαιμία
ΟΜΛ οξεία μυελογενής λευχαιμία
ΚΝΣ κεντρικό νευρικό σύστημα
CPT carnitine palmityl transferase, παλμυτοϊλ τρανσφεράση καρνιτίνης
PPAR υποδοχείς ενεργοποίησης ανάπτυξης περοξεισωμάτων
RAR υποδοχείς ρετινοεικού
TRΗ υποδοχείς θυροειδικής ορμόνης
SRΗ υποδοχείς στεροειδών ορμονών
IL ιντερλευκίνη
TNF παράγοντας νέκρωσης όγκου
LC L-καρνιτίνη
CAT I ακύλ-τρανσφεράση καρνιτίνης Ι
CAT II ακύλ-τρανσφεράση καρνιτίνης Ι
FFA free fatty acids ελεύθερα λιπαρά οξέα (ΕΛΟ)
VLCFA very low chain free fatty acids πολύ χαμηλής αλύσου ΕΛΟ
PDH πυροσταφυλική αφυδρογονάση
LDL low density lipoproteins, χαμηλής πυκνότητας λιποπρωτεϊνες
HDL hight density lipoproteins, υψηλής πυκνότητας λιποπρωτεϊνες
FFA ή NEFA free fatty acids, non esterificate free fatty acids
ελεύθερα λιπαρά οξέα , μη εστεροποιημένα ελεύθερα λιπαρά οξέα
AMP μονοφωσφορική αδενοσίνη
ADP διφωσφορική αδενοσίνη
NADH reduced nicotinamide adenine dinucleotide
FADH2 reduced flavin adenine dinucleotide
BMI Body mass index, δείκτης μάζας σώματος
NSS μη στατιστικά σημαντικό
KB ketone bodies, κετονοσώματα
N αριθμός, πλήθος
TAGs triacylglycerols, τριακύλ γλυκερόλες
DAGs diacylglycerols, διακύλ γλυκερόλες
TG τριγλυκερίδια
T2 μιτοχονδριακή θειολάση του ακετοακυλ- CoA
Βασικές
|
Search
