Test Id : PHLDF

This test includes a charge for the probe application, analysis, and professional interpretation of results for 7 probe sets (14 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.

The Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel includes testing for the following four kinase-activating chromosome rearrangements, as well as for IKZF1 deletion, which often accompanies Ph-like ALL:

1q25 rearrangement, ABL2

5q32 rearrangement, PDGFRB

9p24.1 rearrangement, JAK2

9q34 rearrangement, ABL1

7p-, IKZF1/CEP7

t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement

t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement

When a CRLF2 rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) cryptic translocation.

For more information see B-Lymphoblastic Leukemia/Lymphoma Algorithm.

This test is intended to be ordered when the entire Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like B-cell ALL) fluorescence in situ hybridization (FISH) panel is needed.

If this test is ordered concurrently with either BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies, this test will be canceled. The probes offered in this test are included within BALAF and BALPF, when appropriate.

If this test is ordered and the laboratory is informed that the patient is on a Children's Oncology Group (COG) protocol, this test will be canceled and automatically reordered by the laboratory as COGBF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Children's Oncology Group Enrollment Testing, FISH, Varies.

If limited Ph-like B-cell ALL FISH probes are preferred, order BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies.

At diagnosis, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and a complete B-ALL FISH panel, either BALAF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Adult, Varies or BALPF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), FISH, Pediatric, Varies, depending on the age of the patient, should be performed.

At follow-up, conventional cytogenetic studies (CHRBM / Chromosome Analysis, Hematologic Disorders, Bone Marrow) and targeted B-ALL FISH probes can be evaluated based on the abnormalities identified in the diagnostic study. Order BALMF / B-Cell Acute Lymphoblastic Leukemia/Lymphoma (ALL), Specified FISH, Varies and request specific probes or abnormalities.

If the patient clinically relapses, a conventional chromosome study may be useful to identify cytogenetic changes in the neoplastic clone or the possible emergence of a therapy-related myeloid clone.

For patients with B-cell lymphoma, order BLPMF / B-Cell Lymphoma, Specified FISH, Varies.

For testing paraffin-embedded tissue samples from patients with B-cell lymphoblastic lymphoma, order BLBLF / B-Cell Lymphoblastic Leukemia/Lymphoma, FISH, Tissue. If a paraffin-embedded tissue sample is submitted for this test, testing will be canceled and BLBLF will be added and performed as the appropriate test.

Advise Express Mail or equivalent if not on courier service.

A reason for testing and a flow cytometry and/or a bone marrow pathology report should be submitted with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed in the absence of this information. If not provided, an appropriate indication for testing may be entered by Mayo Clinic Laboratories.

Submit only 1 of the following specimens:

Preferred

Specimen Type: Bone marrow

Container/Tube:

Preferred: Yellow top (ACD)

Acceptable: Green top (heparin) or lavender top (EDTA)

Specimen Volume: 2-3 mL

Collection Instructions:

1. It is preferable to send the first aspirate from the bone marrow collection.

2. Invert several times to mix bone marrow.

3. Send bone marrow specimen in original tube. Do not aliquot.

Acceptable

Specimen Type: Blood

Container/Tube:

Preferred: Yellow top (ACD)

Acceptable: Green top (heparin) or lavender top (EDTA)

Specimen Volume: 6 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send whole blood specimen in original tube. Do not aliquot.

• B-Lymphoblastic Leukemia/Lymphoma Algorithm

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request (T726) with the specimen.

Blood: 2 mL

Bone Marrow: 1 mL

Detecting a neoplastic clone associated with Philadelphia chromosome-like acute lymphoblastic leukemia (ALL), particularly when a classic abnormality is not detected with the initial panel

An adjunct to conventional chromosome studies in patients with B-cell ALL

Evaluating specimens in which standard cytogenetic analysis is unsuccessful

This test includes a charge for the probe application, analysis, and professional interpretation of results for 7 probe sets (14 individual fluorescence in situ hybridization [FISH] probes). Additional charges will be incurred for all reflex or additional probe sets performed.

The Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) panel includes testing for the following four kinase-activating chromosome rearrangements, as well as for IKZF1 deletion, which often accompanies Ph-like ALL:

1q25 rearrangement, ABL2

5q32 rearrangement, PDGFRB

9p24.1 rearrangement, JAK2

9q34 rearrangement, ABL1

7p-, IKZF1/CEP7

t(Xp22.33;var) or t(Yp11.32;var), CRLF2 rearrangement

t(Xp22.33;var) or t(Yp11.32;var), P2RY8 rearrangement

When a CRLF2 rearrangement is identified, reflex testing will be performed using the CRLF2/IGH fusion probe set to identify a potential t(X;14)(p22.33;q32) or t(Y;14)(p11.32;q32) cryptic translocation.

For more information see B-Lymphoblastic Leukemia/Lymphoma Algorithm.

In the United States, the incidence of acute lymphoblastic leukemia (ALL) is roughly 6000 new cases per year (as of 2019). ALL accounts for approximately 70% of all childhood leukemia cases (ages 0-19 years), making it the most common type of childhood cancer. Approximately 85% of pediatric cases of ALL are of B-cell lineage (B-ALL) and 15% are of T-cell lineage (T-ALL). It has a peak incidence at 2 to 5 years of age. The incidence decreases with increasing age, before increasing again at around 50 years of age. ALL is slightly more common in male patients than female patients. There is an increased incidence of ALL in individuals with Down syndrome, Fanconi anemia, Bloom syndrome, ataxia telangiectasia, X-linked agammaglobulinemia, and severe combined immunodeficiency. The overall cure rate for ALL in children is about 90% and about 45% to 60% of adults have long-term disease-free survival. CRLF2/IGH rearrangements are more commonly observed in patients with Down syndrome or of Hispanic descent.

Specific genetic abnormalities are identified in the majority of cases of B-ALL, either by conventional chromosome studies or fluorescence in situ hybridization (FISH) studies. Each of the B-ALL genetic subgroups are important to detect and can be critical prognostic markers. The decision for early transplantation may be made if t(9;22)(q34;q11.2), MLL (KMT2A) translocations, RUNX1 duplication/amplification (iAMP21) or a hypodiploid clone is identified. In contrast, if the ETV6/RUNX1 fusion is detected by FISH or hyperdiploidy is identified by chromosome studies, the patient has a favorable prognosis and transplantation is rarely considered.

A newly recognized World Health Organization entity BCR-ABL1-like ALL, also known as Philadelphia chromosome-like acute lymphoblastic leukemia, is increasing in importance due to the poor prognosis seen in pediatric, adolescent, and young adult ALL. Common features of this entity involve rearrangements with tyrosine kinase genes involving the following genes: ABL2, PDGFRB, JAK2, ABL1, CRLF2, and P2RY8. Deletion of IKZF1 often accompanies this entity. Some patients who have failed conventional therapies have demonstrated favorable responses to targeted therapies in clinical trials when rearrangements involving these specific gene regions have been identified.

Per National Comprehensive Cancer Network guidelines, a combination of cytogenetic and FISH testing is currently recommended in all pediatric and adult patients with B-ALL/lymphoblastic lymphoma.

An interpretive report will be provided.

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 a neoplastic disorder.

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

Fluorescence in situ hybridization (FISH) is not a substitute for conventional chromosome studies because the latter detects chromosome abnormalities associated with other hematological disorders that would be missed by this FISH panel test.

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).

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. Each probe set was evaluated to confirm the probe set detected the abnormality it was designed to detect.

1. Moorman AV, Harrison CJ, Buck GA, et al: Karyotype is an independent prognostic factor in adult acute lymphoblastic leukemia (ALL): analysis of cytogenetic data from patients treated on the Medical Research Council (MRC) UKALLXII/Eastern Cooperative Oncology Group (ECOG) 2993 trial. Blood. 2007 Apr 15;109(8):3189-3197

2. Moorman AV: The clinical relevance of chromosomal and genetic abnormalities in B-cell precursor acute lymphoblastic leukemia. Blood. Rev. 2012 May;26(3):123-135

3. Roberts KG, Li Y, Payne-Turner D, et al: Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia. N Engl J Med. 2014 Sept;371(11):1005-1015

4. Mullighan CG: The genomic landscape of acute lymphoblastic leukemia in children and young adults. Hematology Am Soc Hematol Educ Program. 2014 Dec 5;2014(1):174-180

5. Arber DA, Orazi A, Hasserjian R, et al: The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-2405

This test is performed using commercially available and laboratory-developed probes. Deletion of IKZF1 on chromosome 7 is detected using enumeration strategy probes. Rearrangements involving ABL2, PDGFRB, JAK2, ABL1, CRLF2, and P2RY8 are detected using a dual-color break-apart (BAP) strategy probe. A dual-color, dual-fusion fluorescence in situ hybridization (D-FISH) strategy probe set is used to detect t(X/Y;14). For enumeration and BAP strategy probe sets, 100 interphase nuclei are scored; 200 interphase nuclei are scored when D-FISH probes are used. Results are expressed as the percent abnormal nuclei.(Unpublished Mayo method)

Monday through Friday

• Authorized users can sign in to Test Prices for detailed fee information.
• Clients without access to Test Prices can contact Customer Service 24 hours a day, seven days a week.
• Prospective clients should contact their account representative. For assistance, contact Customer Service.

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. It has not been cleared or approved by the US Food and Drug Administration.

88271x14, 88275x7, 88291 x1-FISH Probe, Analysis, Interpretation; 7 probe sets

88271x2, 88275x1-FISH Probe, Analysis; each additional probe set (if appropriate)