Cancer Mutations also reveal how to treat your cancer

Because medicines today target these mutations

In fact, Molecular testing for Cancer is routinely done for everyone

Blood cancer: Leukemia and other Hematological Malignancies

Diagnose genetic mutations

Leukemias are cancers of blood cells that occur due to various genetic mutations. Testing these mutations are predominantly done by cytogenetics (karyotyping), FISH or flow cytometry using bone marrow aspirate (BMA). Advanced testing by molecular diagnostics offer much superior sensitivity and accuracy with the added benefit of testing on peripheral blood instead of invasive BMA. With molecular tests, cancer mutations can not only be detected, but also monitored regularly in blood for therapy response and early relapse.

Quantify the cancer burden

Quantify to stratify on risk and tailor therapy. After diagnosis, quantitation of the cancer burden helps classify patients based on risk, and plan treatment protocols accordingly. It is important to quantify the cancer burden at diagnosis and to regularly assess it during therapy and after. Moreover, various therapies and procedures, such as bone marrow transplantation are decided and timed based on quantitative tests.

Monitor to remain safe

Monitor regularly using blood to detect early relapse and plan therapy or transplantation. Regularly monitoring the response to therapy identifies development of resistance to treatment and enables early therapy modification. After successful treatment when no cancer mutations are detected by quantitation, it is known as remission. Regular monitoring during this period detects early relapse of the same cancer, which occurs in a majority of patients. Significantly higher sensitivity detects even small changes at an early stage, which can be used for early treatment modifications improving longevity and survival rates.

Easy Samples: Most of our Molecular tests use Blood

Bone marrow aspiration biopsy is mostly NOT required

ALL: Acute Lymphoblastic Leukemia

ALL is the more common leukemia and predominantly affects children. Fighting it intelligently means to diagnose the molecular mutations early and providing targeted treatment.

There are various chromosomal translocations associated with ALL that are able to risk-stratify patients and provide them personalized treatment dramatically improving survival rates.

In addition, mutations such as IKZF1 and ERG deletions can be detected ONLY by molecular tests providing not only improved risk association but also predictive and curative therapy guidance.

Of two forms, B-cell and T-cell, we have molecular markers covering most markers in B-cell ALL and T-cell ALL.

AML: Acute Myeloid Leukemia

The blood cancer with arguably the most varied mutation landscape, AML requires precise testing and diagnostics to improve treatment and cure. Also occurring predominantly in children, chromosomal translocations occur in only 40% of the patients.

The majority are called KN (for karyotype normal) and will need molecular testing for accurate diagnosis of mutations in NPM1, FLT3 and DNMT3A. Mutations in these genes occur in a majority of the patients and stratify them by risk. In addition there’s now targeted medicines available for FLT3 mutations.

While four common molecular markers cover 40% of AML patients, we also offer NPM1, FLT3 and DNMT3A mutations with high coverage, and WT1 quantitation which boosts this coverage to up to 95% of the cases.

CML and ABL1 Resistance Mutations

Everyone with Chronic Myeloid Leukemia (CML) have the BCR-ABL1 genetic mutation. Diagnosing this marker is crucial to initiate therapy with tyrosine kinase inhibitors such as Imatinib.

CML can occur in adults and occasionally in children. People with CML require molecular testing regularly because there are various advanced targeted treatment available today that can lead to ‘cure’. Many people with CML using such molecular diagnostics overcome the cancer and survive as long as people without cancer.

CML patients should test from the beginning and routinely for ABL1 resistance mutations, because anti-ABL1 drugs are used to treat CML. In patients with certain mutations in ABL1, these drugs are ineffective. However, other more effective treatment can be given based on early diagnosis of these mutations by PCR.

Myeloproliferative Neoplasm (MPN)

MPNs have a separate and distinct set of characteristic mutations. These patients also require accurate testing to benefit from personalized treatment regimens and dramatically improved survival rates.

There are three diseases under MPNs the majority of all of which have a specific mutation in JAK2. Identifying this mutation is essential to initiate therapy with JAK2 inhibitors such as ruxolitinib.

  • Polycythemia vera (PV): 95% patients have JAK2 V617F mutation
  • Essential Thrombocythemia (ET): 50-60% patients have JAK2 V617F mutation
  • Primary Myelofibrosis (PMF): 50-60% patients have JAK2 V617F mutation

CMPD panel

 t(9;22)(q34;q11) BCR-ABL1 p210 (2 variants)
JAK2 V617F

CML

 t(9;22)(q34;q11) BCR-ABL1 p210 (2 variants)

ABL TKI Mutation panel

 Tyrosine Kinase Resistance mutations in ABL1 TKD
6 mutations: G250E, Y253F/H, E255K/V, T315I

JAK2

 JAK2 V617F

Myelodysplastic syndrome (MDS)

There are various diseases comprising MDS such as refractory anemia, refractory cytopenia etc. Patients with MDS progress to leukemia, specifically AML, sooner or later. All of them will overexpress WT1 at this stage. So measuring WT1 expression is used as an important marker for monitoring MDS disease progression to leukemia.

MDS can progress into AML and it’s safer to diagnose it as early as possible for highest treatment success. WT1 overexpression is a robust genetic test to be used in this case.

B-ALL Translocations panel

 t(12;21)(p13;q22) ETV6-RUNX1
t(1;19)(q23;p13.3) TCF3-PBX1
t(9;22)(q34;q11) BCR-ABL1 (3 variants)
t(4;11)(q21;q23) MLL-AF4 (6 variants)

T-ALL panel

 del(1p32) SIL-TAL1
TLX3 (HOX11L2) expression, t(5;14)(q35;q32), quantitative
TLX1 (HOX11) expression, t(10;14)(q24;q11), quantitative

IKZF1-ERG deletions (for B-ALL)

 For prognostication, risk-stratification and therapy management
B-cell ALL patients

AML Translocations panel

 t(8;21)(q22;q22) RUNX1-RUNX1T1
inv(16)(p13.1;q22) / t(16;16) CBFB-MYH11 (3 variants)
t(15;17)(q22;q21) PML-RARA (3 variants)

FiND panel (FLT3-NPM1-DNMT3A)

 FLT3 ITDs (exon 14, exon 15, intron 14), FLT3 TKDs (3 mutations)
NPM1 (3 mutations: A, B, D)
DNMT3A (5 mutations: R882X)

WT1 (AML or MDS)

 WT1 quantitative