Haematological & molecular profile of acute myelogenous leukaemia in India.
OBJECTIVE
Recurrent balanced translocations are generally recognized to be a major parameter for prognostication in acute myeloid leukaemia (AML). The chromosomal translocation t(15;17) results in PML/RARalpha fusion gene, t(8;21) results in AML1/ETO fusion gene and Inv 16 generates CBFbeta/MYH11 fusion gene. Patients with these mutations have a good prognosis unlike abnormalities in chromosome 5 or 7 or FLT3 genes. Therefore, we screened the AmL patients for known specific genetic abnormalities that could lead to more definitive prognoses.


METHODS
A total of 113 AML patients were evaluated at diagnosis based on routine morphology and cytochemistry and classified according to the WHO criteria. The distribution of AML subtypes was M1(1), M2(32), M3(57), M4(14), M5(1), M6(1) and seven cases where morphological subtype could not be classified. RT-PCR was performed to identify PML/RARalpha, AML1/ETO, CBFbeta/MYH11 and FLT3 nternal tandem duplication (ITD).


RESULTS
Of the 57 patients with M3 subtype, 55 had the PML-RARalpha fusion transcript. The prevalence of bcr3 (short isoform) was higher (62%) than that of bcr1 (long isoform) (38%) and no correlation was found with age, sex or white blood cell count. FLT3 internal tandem duplication (ITD) mutations were more frequent in patients with APL than in other AML subtypes (17.5 vs. 8.9%), the frequency greater in patients with bcr3 isoform (70%) than in those with in bcr1 isoform (30%). Patients with FLT3/ ITD mutations had a significantly higher median white cell count than those without these mutations (55 x 10(9)/l vs. 6.3 x 10(9)/l P<0.001). More patients with FLT3/ITD mutations died early (53%) than those without these mutations (16%) (P<0.01). AML1-ETO fusion transcript was detected in 16 of 56 patients with no correlation with clinical or haematological parameters.


CONCLUSIONS
The results of the present study showed presence of bcr3 (short isoform) higher than bcr1 (long isoform). FLT3 internal tandem duplication (ITD) mutation was predominant in acute promyelocytic leukaemia patients with bcr3 isoform. Thus, patients with APL who have FLT3 mutation appear to have a poorer prognosis. Therefore, rapid identification of specific translocations at diagnosis is important for prognostic purposes and their detection should be incorporated into routine assessment.
Sazawal
Sudha
S
Department of Haematology, All India Institute of Medical Sciences, New Delhi, India.
Kumar
Bijender
B
Hasan
Syed Khizer
SK
Dutta
Pankhi
P
Kumar
Rajat
R
Chaubey
Rekha
R
Mir
Rashid
R
Saxena
Renu
R
D000293:Adolescent; D000328:Adult; D002648:Child; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D005260:Female; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D007194:India / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015995:Prevalence; D011379:Prognosis; D000075142:RUNX1 Translocation Partner 1 Protein; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014178:Translocation, Genetic; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics
C107844:AML1-ETO fusion protein, human; C095514:CBFbeta-MYH11 fusion protein; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; C093476:promyelocytic leukemia-retinoic acid receptor alpha fusion oncoprotein; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3