1 case of Philadelphia chromosome after relapse of chromosomal negative acute myeloid leukemia in Philadelphia

Philadelphia chromosomes from chromosomes 9 and 22 translocation to form a specific Ph chromosome and with tyrosine kinase activity Of BCR -ABL fusion protein, is an important cellular genetic marker of chronic granulocytic leukemia? In addition, Ph chromosomes are also common in high-risk acute leukemia?acute myeloid leukemia (myeloid leukemia, AML) patients with Ph chromosomes clinically rare, detection rate of only about 0.5% to 3.0% Low incidence of Ph-positive AML, low mitigation rate, poor prognosis? Ph-negative AML re-emergence as Ph-positive AML is extremely rare, no relevant reports have been found in China?1 case datapatient, male, 66 years old? In September 2015 due to "fever? fatigue more than 20 days" in the local hospital, check the blood routine: white blood cells 1.3 x 10 9/L, red blood cells 2.09 x 1012/L, hemoglobin 69g/L, platelet 54 x 10 9/L? The original infant single accounted for 37%?flow cytokine immune type: early myelin cell accounted for 31.92%, expression CD117, CD33, CD34, CD123, HLA-DR, CD64, CD38, CD13, MPO, sub-table CD15? second-generation sequencing technology to detect AML 42 related gene mutations (DNA) did not detect mutations? PCR detects 30 types of chromotherapy causes (including BCR-ABL190 and BCR - ABL210) are negative? Chromosome nuclear types: 47, XY, s8? Diagnosed with acute monocyacyamy? Complete remission after chemotherapy on 4 October 2015 for dA? 2015 - 11-2016 - 10 consecutive DA? Aa? Aa? MA? MD-Ara-C solution solid 5 cycles, during the review of bone wear original infant single are less than 5%, flow cytokine detection of small residual leukemia (MRD) abnormal myeloid cells fluctuations in about 0.2%? December 30, 2016 review of bone marrow image: bone marrow has nuclear cells hyperplasia significantly active, the original infant accounted for 6.5%? MRD: Original? Infantmyel cells 10.1%, immune phenotypes are CD34 (-), CD117 (?), CD33 (plus), HLA-DR (?), CD13 (plus), CD36 (-), CD64 (?) -), CD14 (-), CD56 (-)? Disease recurrence, again given 2 cycles of DA protocol induced treatment, did not reach a complete relief? 2017 - 04- 2017 - 11 phase to IA? DCAG?HA? DCAG? DCHG program chemotherapy, during the period of multiple re-examination of bone marrow like the original cell fluctuations in 6.0% to 13.5%, flow-micro-cell detection MRD abnormal myelin cell fluctuations in 3% to 10%? December 2017 review of bone marrow image: the original infant single accounted for 16%, flow cell detection MRD abnormal myelin cells accounted for 26.7%? January 2018 due to lung infection in my hospital, physical examination: shallow gonorerin knots not touched the swelling, chest bone no tenderness, double lung smell and wet sound, Blood routine: white blood cell 23.15 x 10 9 / L, red blood cell 3.58 x 1012/L, hemoglobin 104g/L, platelet 334 x 10 9/L? bone marrow like: bone marrow has nuclear cell hyperplasia, raw mononucleocell accounted for 12.2%, infantile monocyte accounted for 5.6%? Flow cytokine detection MRD: Abnormal myelin cells accounted for 37.08%, immunothtype: CD34 (-) CD117 (-) CD13 (-) CD56 (-) HLA-DR (-) CD15 (-) CD14 (-) CD64 (-) CD19 (-) CD7 (part plus) CD45 (dim)? Second generation sequencing technology detects 42 related gene mutations (DNA) in AML do not find gene mutations? Leukemia-related fusion gene screening qualitative test (43): BCR-ABL190 positive? PCR Detection BCR - ABL190: ABL 9.93 x 10 5 copy/ml; BCR-ABL 190 5.82 x 10 4 torture/ml; BCR-ABL190/ABL 58.61%; PCR detection BCR-ABL210 show: ABL 1.57 x 10 5 copy/ml; BCR-ABL210 below the minimum detection limit torture/ml; BCR-ABL210/ABL below minimum detection limit; IS below minimum detection limit? Fluorescent in situ hybridization (FISH) test t (9;22) BCR-ABL positive?chromosome nuclear type analysis: 47, XY, s8, t (9;22) (q34; q11) ? 10? Diagnosed as relapsing incurable AML with BCR-ABL? Give hydroxyurea reduction of aluke cells? Alkaline urine and anti-infection treatment, after the lung infection improves, give Imartinib 400mg qd oral? February 22, 2018 review of bone marrow like: bone marrow has nuclear cells hyperactivity, raw mononucleoblasts 5.8%, childish mononucleoblasts 6.6%? Flow cytokine detection MRD: Abnormal myelin primary cells accounted for 32.04%? Fusion gene detected BCR-ABL190/ABL is 21 .90%? Patients' MRD decreased from the previous course of treatment, did not appear fever and other symptoms of infection, continue to give Imatinib 400 mg qd mouth service, while giving rename? Co-e-recombinant interferon alpha - 1b? leukocyte interleukin-2 regulatory immunotherapy, April 2018 due to lung infection death?2 DiscussionPh chromosome is a common cytogenetic abnormality, can be found in most chronic granulocytic leukemia? Part of acute lymphocytic leukemia and a small number of AML?t (9;22) tired of 9q34 on the BCR primary cancer gene and 22q11 aBL primary cancer gene, the formation of BCR-ABL fusion gene, coding a tyrosine enzyme active protein (4?) In 2016, WHO took Ph-positive AML as a new subtype of AML: no chronic and accelerated history of chronic granulocytic leukemia, a fab fractionoftype for AML, flow cytocytic undetected gonorrhea antigen expression, cytogenetics and molecular biology detected Ph chromosomes and/or BCR-ABL fusion genes (5-6)? Phyang AML mainly occurs in AML with NPM1 mutation? Core junction factor correlation acute myeloid leukemia (CBF-AML) and AML with bone marrow hyperplasia ( 7)? In patients with Ph-negative AML, ph chromosomes are less than 0.1% (8) in AML patients, and tend to occur in CBF-AML (9-10)? Shah et al(10) found that Ph-negative AML progression of Ph-positive AML patients, Ph chromosome seq.tsic 10 to 53 months after initial diagnosis, generally in the first recurrence? 2nd recurrence or disease terminal? Chen et al(11) reported 3 cases of long-term Ph chromosome AML patients, found that the long-term ph chromosome is more tending to occur in the progression of the disease and recurrence, most patients relapse with other chromosomal abnormalities in addition to the Ph chromosome?the occurrence of ph chromosomes in this patient in the long-term recurrence, reminding us to consider the occurrence of secondary cloning when treating multiple recurrences after AML remission? In this case, 11 patients with Ph-positive AML progress iepositive ph-positive AML were detected in 11 patients with Ph-positive AML, and only 1 MDS-converted AML patient was detected in 11 patients with Ph-positive AML after the presence of Ph chromosomes At the same time, BCR-ABL190 and BCR-ABL210 were detected? Combined with this example and related reports, we can conclude that the AML forward ph chromosome BCR-ABL190 clone is more common than BCR-ABL210 (10-12)? AML patients relapse after the emergence of Ph chromosomes, it is believed that there are 3 possible explanations, one is at the initial diagnosis of Ph-positive cells already exist, due to the cell in the middle of fissure or Ph-positive cell number is too low, the existing technology can not be detected, long-term chemotherapy makes the patient's body Ph-negative cloning gradually decreased, and Ph-positive kronon in selective pressure gradually proliferating and screening out; FLT3 - ITD? c - KIT, etc.) the proliferation or survival advantage of hematopoietic stem cells; Class II mutations (e.gPML-RARa?) AML-ETO? MLL, etc.) caused by inhibition of hematopoietic differentiation and apoptosis? The long-term emergence of ph chromosomes may further explain aML's multi-step morbidity and multiple-strike mechanism (7,13); At present, it is considered that the overall prognosis of Ph-positive AML is not good, such diseases have a poor response to chemotherapy in the ring and alyghasine? Neuendorff et al(7) summarized 7 cases of patients receiving relapsed refractive AML with BCR-ABL patients receiving tyrosine kinase inhibitor (TKI) treatment, and found that 3 patients were cleared of Ph-positive cloning? TKI can specifically inhibit BCR-ABL expression, block cell signal transduction, inhibit BCR-ABL-positive cell proliferation, and induce apoptosis? TKI as a first-line program and rescue treatment plan can make Ph-positive AML get good results, induced chemotherapy after complete remission of the application of TKI class for maintenance therapy, can obtain 10 to 19 months of complete remission (14)? Early application of TKI combined chemotherapy, complete remission as early as possible hematopoietic stem cell transplantation, can effectively improve the prognosis (15-17)?references