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


Advisory Information


This test is only performed on specimens from pediatric patients being considered for enrollment in a Children's Oncology Group (COG) protocol. For all other patients, order TALLF / T-Cell Acute Lymphoblastic Leukemia (T-ALL), FISH, Varies.

 

This test should not be ordered on blood and bone marrow specimens from patients with T-cell lymphoma. In these situations, order TLPF / T-Cell Lymphoma, FISH, Blood or Bone Marrow.



Shipping Instructions


Advise Express Mail or equivalent if not on courier service.



Necessary Information


1. Provide a reason for referral with each specimen as well as flow cytometry and/or a bone marrow pathology report and Children's Oncology Group (COG) protocol number. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.

2. If a child enrolled in the COG protocol has received an opposite sex bone marrow transplant prior to specimen collection, convey this information to the laboratory.



Specimen Required


Submit only 1 of the following specimens:

 

Preferred Specimen Type: Bone marrow

Container/Tube: Green top (sodium heparin)

Specimen Volume: 1 to 2 mL

Collection Instructions:

Invert several times to mix bone marrow.

 

Acceptable Specimen Type: Blood

Container/Tube: Green top (sodium heparin)

Specimen Volume: 6 mL

Collection Instructions:

Invert several times to mix blood.


Useful For

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.

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
_I099 Interphases, 25-99 No, (Bill Only) No
_I300 Interphases, >=100 No, (Bill Only) No
_IL25 Interphases, <25 No, (Bill Only) No
_PADD Probe, +1 No, (Bill Only) No
_PB02 Probe, +2 No, (Bill Only) No
_PB03 Probe, +3 No, (Bill Only) No
_PBCT Probe, +2 No, (Bill Only) No

Testing Algorithm

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.

Method Name

Fluorescence In Situ Hybridization (FISH)

Reporting Name

COG, ALL (T-cell), FISH

Specimen Type

Varies

Specimen Minimum Volume

Blood: 2 mL
Bone Marrow: 1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
  Refrigerated 

Clinical Information

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 (≥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

An interpretive report will be provided.

Interpretation

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.

Clinical Reference

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

Day(s) and Time(s) Performed

Specimens are processed Monday through Sunday.

Results reported Monday through Friday, 8 a.m.-5 p.m.

Analytic Time

7 days

Test Classification

This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

88271 x 2, 88291-DNA probe, each (first probe set), Interpretation and report

88271 x 2-DNA probe, each; each additional probe set (if appropriate)

88271-DNA probe, each; coverage for sets containing 3 probes (if appropriate)

88271 x 2-DNA probe, each; coverage for sets containing 4 probes (if appropriate)

88271 x 3-DNA probe, each; coverage for sets containing 5 probes (if appropriate)

88274 w/modifier 52-Interphase in situ hybridization, <25 cells, each probe set (if appropriate)

88274-Interphase in situ hybridization, 25 to 99 cells, each probe set (if appropriate)

88275-Interphase in situ hybridization, 100 to 300 cells, each probe set (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
COGTF COG, ALL (T-cell), FISH In Process

 

Result ID Test Result Name Result LOINC Value
602286 Result Summary 50397-9
602287 Interpretation 69965-2
602288 Result Table 93356-4
602289 Result 62356-1
GC016 Reason for Referral 42349-1
GC017 Specimen 31208-2
602291 Source 31208-2
602292 Method 85069-3
602293 Additional Information 48767-8
602294 Disclaimer 62364-5
602295 Released By 18771-6