TEST CATALOG ORDERING & RESULTS SPECIMEN HANDLING CUSTOMER SERVICE EDUCATION & INSIGHTS
Test Catalog

Test ID: COGTF    
T-Cell Acute Lymphoblastic Leukemia (T-ALL), Children's Oncology Group Enrollment Testing, FISH, Varies

Useful For Suggests clinical disorders or settings where the test may be helpful

Evaluation of pediatric bone marrow and peripheral blood specimens by FISH probe analysis for classic rearrangements and chromosomal copy number changes associated with T-cell acute lymphoblastic leukemia (T-ALL) in patients being considered for enrollment in Children's Oncology Group (COG) clinical trials and research protocols.

Testing Algorithm Delineates situations when tests are added to the initial order. This includes reflex and additional tests.

This test is only performed on specimens from pediatric patients who are candidates for enrollment in Children's Oncology Group clinical trials and research protocols.

 

We recommend the following testing algorithm for patients with T-cell acute lymphoblastic leukemia (T-ALL):

-At diagnosis, standard (diagnostic) T-ALL FISH panel and/or conventional chromosome studies COGBM / Chromosome Analysis, Hematologic Disorders, Children's Oncology Group Enrollment Testing, Bone Marrow should be performed. If there is limited specimen available, only the COGTF / T-Cell Acute Lymphoblastic Leukemia (T-ALL), Children's Oncology Group Enrollment Testing, FISH, Varies test will be performed.

 

Panel includes testing for the following abnormalities using the probes listed:

1p33 rearrangement, TAL1/STIL

t(5;14) TLX3/BCL11B

7q34 rearrangement, TRB

9p-, CDKN2A/D9Z1

t(9;22) or ABL1 amplification, BCR/ABL1

t(10;11), MLLT10/PICALM

11q23 rearrangement, MLL (KMT2A)

14q11.2 rearrangement, TRAD

17p-, TP53/D17Z1

 

When an MLL (KMT2A) rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(4;11)(q21;q23) AFF1/MLL, t(6;11)(q27;q23) MLLT4/MLL, t(9;11)(p22;q23) MLLT3/MLL, t(10;11)(p13;q23) MLLT10/MLL, t(11;19)(q23;p13.1) MLL/ELL or t(11;19)(q23;p13.3) MLL/MLLT1.

 

When a TRAD rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(8;14)(q24.1;q11.2) MYC/TRAD, t(10;14)(q24;q11.2) TLX1/TRAD, t(11;14)(p15;q11.2) LMO1/TRAD or t(11;14)(p13;q11.2) LMO2/TRAD.

 

When a TRB rearrangement is identified, reflex testing will be performed to identify the translocation partner. Probes include identification of t(7;10)(q34;q24) TRB/HOX11, t(7;11)(q34;p15) TRB/LMO1, t(7;11)(q34;p13) TRB/LMO2, or t(6;7)(q27;q34) TRB/MYB.

-If this test is ordered and the laboratory is informed that the patient is not on a COG protocol, this test will be canceled and automatically reordered by the laboratory as TALLF / T-Cell Acute Lymphoblastic Leukemia (T-ALL), FISH, Varies.

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

In the United States, the incidence of acute lymphoblastic leukemia (ALL) is roughly 6,000 new cases per year or approximately 1 in 50,000. ALL accounts for approximately 70% of all childhood leukemia cases (ages 0 to 19 years), making it the most common type of childhood cancer. Approximately 85% of pediatric cases of ALL are B-cell lineage (B-ALL) and 15% are T-cell lineage (T-ALL). T-ALL is more common in adolescents than younger children and accounts for 25% of adult ALL. When occurring as a primary lymphoblastic lymphoma (LBL), approximately 90% are T-cell lineage versus only 10% B-cell lineage. T-LBL often present as a mediastinal mass in younger patients with or without concurrent bone marrow involvement.

 

Specific genetic abnormalities are identified in the majority of cases of T-ALL, although many of the classic abnormalities are not detected by conventional chromosome studies and must be identified by FISH studies. Each of the genetic subgroups can be critical prognostic markers. One predictive marker, amplification of the ABL1 gene region, has been identified in 5% of T-ALL, and these patients may be responsive to targeted tyrosine kinase inhibitors.

 

A combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients to characterize the T-ALL clone for the prognostic genetic subgroups. A summary of the characteristic chromosome abnormalities identified in T-ALL are listed in the following table.

 

Common Chromosome Abnormalities in

T-cell Acute Lymphoblastic Leukemia

Cytogenetic change

Genes involved

del(1p33)

TAL1/STIL

t(5;14)(q35;q32)

TLX3(HOX11L2)/BCL11B

t(10;11)(p13;q14)

MLLT10(AF10)/PICALM

Episomal amplification

ABL1

del(9p)

CDKN2A(p16)

t(11q23;var)

MLL(KMT2A)

t(4;11)(q21;q23)

AFF1(AF4)/MLL(KMT2A)

t(6;11)(q27;q23)

MLLT4(AF6)/MLL(KMT2A)

t(9;11)(p22;q23)

MLLT3(AF9)/MLL(KMT2A)

t(10;11)(p13;q23)

MLLT10(AF10)/MLL(KMT2A)

t(11;19)(q23;p13.1)

MLL(KMT2A)/ELL

t(11;19)(q23;p13.3)

MLL(KMT2A)/MLLT1(ENL)

t(7q34;var)

TRB

t(6;7)(q23;q34)

MYB/TRB

t(7;10)(q34;q24)

TRB/TLX1(HOX11)

t(7;11)(q34;p15)

TRB/LMO1

t(7;11)(q34;p13)

TRB/LMO2

t(14q11.2;var)

TRAD

t(8;14)(q24.1;q11.2)

MYC/TRAD

t(10;14)(q24;q11.2)

TLX1(HOX11)/TRAD

t(11;14)(p15;q11.2)

LMO1/TRAD

t(11;14)(p13;q11.2)

LMO2/TRAD

del(17p)

TP53

Complex karyotype (> or =4 abnormalities)

 

 

Metaphase FISH confirmation of classic translocations that are cryptic and not visually detectable by chromosome analysis (ie, t[12;21] associated with ETV6/RUNX1 fusion) is performed as required by Children's Oncology Group (COG) and is included as part of the electronic case submission by the Mayo Clinic Genomics Laboratory to COG for central review.

 

Additional cytogenetic techniques such as chromosomal microarray (CMAH / Chromosomal Microarray, Hematologic Disorders, Varies) may be helpful to resolve questions related to ploidy (hyperdiploid clone vs doubled hypodiploid clone) or to resolve certain clonal structural rearrangements such as the presence or absence of intrachromosomal amplification of chromosome 21 (iAMP21). Occasionally, characterization of balanced or complex rearrangements presumed to involve critical genes (such as a kinase activating gene and a fusion partner) may be characterizable by Mate Pair sequencing (MTRBM / MatePair, Targeted Rearrangements, Hematologic, Varies); a clinically validated next generation sequencing technique developed at Mayo Clinic.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Interpretation Provides information to assist in interpretation of the test results

A neoplastic clone is detected when the percent of cells with an abnormality exceeds the normal reference range for any given probe.

 

The absence of an abnormal clone does not rule out the presence of neoplastic disorder.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test is not approved by the U.S. Food and Drug Administration and it is best used as an adjunct to existing clinical and pathologic information.

 

Bone marrow is the preferred specimen type for this FISH test. If bone marrow is not available, a blood specimen may be used if there are malignant cells in the blood specimen (as verified by a hematopathologist).

Supportive Data

Each probe was independently tested and verified on unstimulated peripheral blood and bone marrow specimens. Normal cutoffs were calculated based on the results of 25 normal specimens. For each probe set a series of chromosomally abnormal specimens was evaluated to confirm each probe set detected the abnormality it was designed to detect.

Clinical Reference Recommendations for in-depth reading of a clinical nature

1. Swerdlow SH, Campo E, Harris NL, et al.: International Agency for Research on Cancer (IARC): World Health Organization (WHO) classification of tumours of haematopoietic and lymphoid tissues. IARC Press, Oxford University Press, 2017

2. Gesk S, Martin-Subero JI, Harder L, et al: Molecular cytogenetic detection of chromosomal breakpoints in T-cell receptor gene loci. Leukemia 2003;17:738-745

3. Chin M, Mugishima H, Takamura M, et al: Hemophagocytic syndrome and hepatosplenic (gamma)(delta) T-cell lymphoma with isochromosome 7q and 8 trisomy. J Pediatr Hematol Oncol 2004;26(6):375-378

4. Graux C, Cools J, Michaux L, et al: Cytogenetics and molecular genetics of T-cell acute lymphoblastic leukemia: from thymocyte to lymphoblast. Leukemia 2006;20:1496-1510

5. Liu Y, Easton J, Shao Y, et al: The genomic landscape of pediatric and young adult T-lineage acute lymphoblastic leukemia. Nat Genet 2017;49(8):1211-1218