Molecular Screening of 28 Genes in Mexican Patients with Acute Myeloid Leukemia a Series of 70 Patients from the Instituto Nacional De Cancerologia, Mexico

Introduction:

Acute Myeloid Leukemia is a clonal heterogeneous disease, where age is an important risk factor to develop theses disease, PCR studies and next generation sequence have proven the diversity of these disease. A lot of genes mutations have been identifying to play a role in the DNA metilation, epigenetics a transcription. We initiate a screening to all acute myeloid leukemias that where the novo or relapse with a 28 gene panel of HEMAVISION a 28q; DNA diagnostic, for the detection al ARN gene fusion and alternatives of the: PML-RAR ALFA (bcr2,V), CBF-MYH11, RUNX1-RUNX1T1, PML-RAR alfa(bcr1,L), KMT2A-MLT3, PML-RAR alfa (bcr3,S), KMT2A-ELL, FUS-ERG, ETV6-MN1, DEK-NUP214, KMT2A-EPS15, KMT2A-AFDN, TCF3-PBX1, ETV6-RUNX1, KMT2A-MLLT1, KMT2A-AFF1, TCF3-HLF, STIL-TAL1, BCR/ABL(p190), SET-NUP214, BCR/ABL(p210), BCR/ABL(p230), ZBTB16-RARalfa, ETV6-ABL1, ETV6-PDGFRB, KMT2A-MLLT10, KMT2A-MLLT11,KMT2A-FOXO4, KMT2A-MLLT6, RUNX1-MECON, NPM1-RAR alfa, NMP1-MLF1, RUNX1-MECON.

FLT3 ITD mutation and D385 by PCR electrophoresis by Invivoscribe was also perform. And the regular cytogenetics and FISH mutations for BCR/ABL, PML/RAR alfa, Inv16, MLL, +8, ETO, BCR, ABL, monosomy 7, monosomy8

Objectives

The main objective is the know the mutation in the Mexican population and the prognostic in these group of patients

Results

These study was perform at Instituto Nacional de Cancerologia, Mexico, randomized patient from 2016-2018 where screen. A total of 70 patients, 37 females and 33 males, ages from 18-85years old, 54 patients where newly diagnosis of acute myeloid leukemia, 4 where relapses and 12 where secondary leukemias, the most frequent FAB morphologic classification where M4:22 cases, M2:15 cases, M3:8 cases, M1:4cases, M0 and M5:3 cases each.

Of the 70 patients: 56 patients where negative to all of the panel screen, FLT3 where only perform in 14 patients 12 where negative and 2 where insufficient to perform the test, the most common FISH translocation was PML/RAR alfa, follow by MLL, ETO and +8.

For the cytogenetics we had 21 cases that didn´t have enough metaphases, 7 normal, 28 cases with more than 2 cytogenetics alterations and 9 with only 1. With a Cytogenetics risk: high risk 44, intermedium:10 and low12.

Of the 70 patient, 14 have some genes mutations +: t(9;11)(p22;q23) KMT2A-MLLT3, t(6;11)(q27;q23) KMT2A-AFDN, t(5;12)(q33;p13) ETV6-PDGFRB, t(8;21)(q22;q22) RUNX1RUNX1T1, inv16(p13q;22q) CBFB-MYH11, t(6;11)(q27;q23) KMT2A-AFDN, t(3;21)(q26:q22) RUNX1-MECOM, inv16(p13q;22q) CBFB-MYH11, t(15;17)(q24;q21) PML-RARA (bcr2,V) t(15;17)(q24;q21) PML-RARA (bcr1,L) t(15;17)(q24;q21) PML-RARA (bcr3,S), t(8;21)(q22;q22) RUNX1RUNX1T1, t(8;21)(q22;q22) RUNX1RUNX1T1, t(15;17)(q24;q21) PML-RARA (bcr3,S)

Out of 70 patients: 38 receive 7+3 (cytarabine + Daunorubicin) for first line of treatment, 41 received high doses of cytarabine at 3g /m2. Our first option for relapse treatment is MEC (mitoxantrone, cytarabine and etoposide) because of costs and the second line of rescued treatment is Flag- Ida (idarubicin, fludarabine and cytarabine) and not all patient can afford it.

For the elderly patients the first line of treatment is low dose of cytarabine and only in those who can pay azacytidine it is use.

The correlation between high risk cytogenetics with mortality is 12 cases out 70. And genes with morality only 4 patients with: t(9;11)(p22;q23) KMT2A-MLLT3, t(6;11)(q27;q23) KMT2A-AFDN, t(5;12)(q33;p13) ETV6-PDGFRB, t(6;11)(q27;q23) KMT2A-AFDN

Conclusion

We need to know our population characteristics, we don´t have the incidence and prevalence of the gene mutation in the Mexican population. In the market there are several screening panels with different genes. We need to have more genes and more patient to be analyzed to learn our molecular risk, to have a better approach to these patients and better techniques.

There is no paper publish with the genetics and gene alteration in the Mexican Population, it is important to continuing working and to use panels with genes as ASXL1, FLT-TKD, CEBPA, KIT, KRAS, IDH1,2, TET2 and others.

And other important issue that we found is the high number of patient that abandon treatment 4 cases, because of money issues. And the time of these population 24 patient where death.

The incidence of FLT3 mutation ITD and D385 is low in theses population but it was performed only 14/70 patients, we need a large number of patient to know the real incidence.

Table.

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